Miracle-dz/UniFAR-FTUs huggingface dataset:
Diffusion rather than intraflagellar transport likely provides most of the tubulin required for axonemal assembly in Chlamydomonas

ABSTRACT Tubulin enters the cilium by diffusion and motor-based intraflagellar transport (IFT). However, the respective contribution of each route in providing tubulin for axonemal assembly remains unknown. Using Chlamydomonas, we attenuated IFT-based tubulin transport of GFP–β-tubulin by altering the IFT74N–IFT81N tubulin-binding module and the C-terminal E-hook of tubulin. E-hook-deficient GFP–β-tubulin was incorporated into the axonemal microtubules, but its transport frequency by IFT was reduced by ∼90% in control cells and essentially abolished when the tubulin-binding site of IFT81 was incapacitated. Despite the strong reduction in IFT, the proportion of E-hook-deficient GFP–β-tubulin in the axoneme was only moderately reduced. In vivo imaging showed more GFP–β-tubulin particles entering cilia by diffusion than by IFT. Extrapolated to endogenous tubulin, the data indicate that diffusion provides most of the tubulin required for axonemal assembly. We propose that IFT of tubulin is nevertheless needed for ciliogenesis, because it augments the tubulin pool supplied to the ciliary tip by diffusion, thus ensuring that free tubulin there is maintained at the critical concentration for plus-end microtubule assembly during rapid ciliary growth. Highlighted Article: Using GFP-tagged β-tubulin, we show that most of the tubulin required for axonemal assembly enters Chlamydomonas cilia by diffusion rather than by intraflagellar transport.
Microgeographic epidemiology of malaria parasites in an irrigated area of western Kenya by deep amplicon sequencing.

To improve food security, investments in irrigated agriculture are anticipated to increase throughout Africa. However, the extent that environmental changes from water resource development will impact malaria epidemiology remains unclear. This study was designed to both compare the sensitivity of molecular markers used in deep amplicon sequencing for evaluating malaria transmission intensities; and assess malaria transmission intensity at various proximities to an irrigation scheme. Compared to ama1, csp, and msp1 amplicons, cpmp required the smallest sample size to detect differences in infection complexity between transmission risk zones. Transmission intensity was highest within five kilometers of the irrigation scheme by PCR positivity rate, infection complexity, and linkage disequilibrium. The irrigated area provided a source of parasite infections for the surrounding 2-10 km area. This study highlights the suitability of the cpmp amplicon as a measure for transmission intensities and the impact of irrigation on microgeographic epidemiology of malaria parasites.
Validity and accuracy of calculating oxidative ATP synthesis in vivo during high‐intensity skeletal muscle contractions

Several methods have been developed for using 31P‐MRS to calculate rates of oxidative ATP synthesis (ATPOX) during muscular contractions based on assumptions that (1) the ATP cost of force generation (ATPCOST) remains constant or (2) Michaelis‐Menten coupling between cytosolic ADP and ATPOX does not change. However, growing evidence suggests that one, or both, of these assumptions are invalid during high‐intensity fatigue protocols. Consequently, there is a need to examine the validity and accuracy of traditional ATPOX calculation methods under these conditions. To address this gap, we measured phosphate concentrations and pH in the vastus lateralis muscle of nine young adults during four rest‐contraction‐recovery trials lasting 24, 60, 120, and 240 s. The initial velocity of phosphocreatine resynthesis (ViPCr) following each trial served as the criterion measure of ATPOX because this method makes no assumptions of constant ATPCOST or Michaelis‐Menten coupling between changes in cytosolic ADP and ATPOX. Subsequently, we calculated ATPOX throughout the 240 s trial using several traditional calculation methods and compared estimations of ATPOX from each method with time‐matched measurements of ViPCr. Method 1, which assumes that ATPCOST does not change, was able to model changes in ViPCr over time, but showed poor accuracy for predicting ViPCr across a wide range of ATPOX values. In contrast, Michaelis‐Menten methods, which assume that the relationship between changes in cytosolic ADP and ATPOX remains constant, were invalid because they could not model the decline in ViPCr. However, adjusting these Michaelis‐Menten methods for observed changes in maximal ATPOX capacity (i.e., Vmax) permitted modeling of the decline in ViPCr and markedly improved accuracy. The results of these comprehensive analyses demonstrate that valid, accurate measurements of ATPOX can be obtained during high‐intensity contractions by adjusting Michaelis‐Menten ATPOX calculations for changes in Vmax observed from baseline to post‐fatigue.
Positional obstructive sleep apnea within a large multicenter French cohort: prevalence, characteristics, and treatment outcomes.

STUDY OBJECTIVES To assess, in a large cohort of patients with obstructive sleep apnea (OSA), the factors that are independently associated with positional OSA (POSA) and exclusive POSA (e-POSA) and determine their prevalence. The secondary objective was to evaluate the outcome of positive airway pressure (PAP) therapy for POSA and e-POSA patients. METHODS This retrospective study included 6,437 typical mild-to-severe OSA patients from the Pays de la Loire sleep cohort. Patients with POSA and e-POSA were compared to those with non POSA (NPOSA) for clinical and polygraphic characteristics. In a subgroup of patients (n=3,000) included in a PAP follow-up analysis, we determined whether POSA and e-POSA phenotypes were associated with treatment outcomes at 6 months. RESULTS POSA and e-POSA had a prevalence of 53.5% and 20.1% respectively and were independently associated with time in supine position, male gender, younger age, lower AHI and lower BMI. After adjustment for confounding factors, patients with POSA and e-POSA had a significantly lower likelihood of treatment adherence (PAP daily use ≥4h) at 6 months and were at higher risk of PAP treatment withdrawal compared to NPOSA. CONCLUSIONS The prevalence and independent predictors of POSA and e-POSA were determined in this large clinical population. POSA and e-POSA patients have lower PAP therapy adherence and this choice of treatment may not be optimal. Thus, there is a need to offer these patients an alternative therapy.
Federalism, National Identity and Overcoming Frozen Conflicts: Moldova's Experience

Abstract In the Republic of Moldova struggles for independence and over national identity in the late 1980s and the early 1990s resulted in two conflicts with the Gagauz minority and separatists in the region of Transnistria. In this paper we compare and contextualize the settlement processes and pay specific attention to Chisinau’s perceptions of the two conflicts. Our analysis highlights how Gagauz autonomy and Transnistrian separatism are situated in the complex relationship between geopolitics and domestic identity politics that reproduces cleavages among Moldova’s political stakeholders. This is a major obstacle to a coherent position of Chisinau and the implementation of autonomy arrangements in both cases.
Molecular diversity of the Metarhizium anisopliae lineage in an agricultural field

Entomopathogenic fungal isolates identified by morphology as Metarhizium anisopliae may belong to different species when identified by molecular characters. We isolated Metarhizium spp. from an experimental agricultural field under both conventional and organic farming regimes using Tenebrio molitor as bait insect to assess the molecular diversity within the soil. Isolates were analyzed using DNA sequencing and applying SSR markers. Within the former M. anisopliae lineage, we found M. brunneum (86.3%), M. robertsii (11.3%) and M. majus (3.4%) in the soil samples. Several genotypes of each species were identified based on SSR markers. Differences in abundance of the species and their genotypes suggest different adaptations to the soil environment of the agricultural field. There were no effects of conventinal or organic farming regimes on diversity of the fungi.
Potassium fertilisers and development: review of major approaches to improve supply

The paper aims to review major approaches to improving potassium fertilizer supply in developing countries and discusses the constraints of the two dominant food system paradigms, industrialized and closed system production, in securing fertilizer supply. The paper describes the current global supply of potassium fertilizers and approaches to improving the supply based on the review of existing literature and industry reports. In order to outline the approaches to supply of potassium, the paper utilizes both supply chain perspective (Marsden et al, 2000; Sonnino and Marsden, 2006) and global production network view (Coe et al, 2008; Bridge, 2008; Dicken, 2011; Santos et al, 2015). The paper discusses how two food systems, industrialized and closed system production, experience difficulties in combating structural limitations of producing organic and inorganic potassium fertilizers for food production. It suggests developing a hybrid system, where capabilities of private actors to supply potassium fertilizers can be utilized for serving the needs of large-scale and small-scale food production.
Molecular characterization of antimicrobial resistance and virulence genes of Escherichia coli isolates from bovine mastitis

Background and Aim: Mastitis is a common and economically important disease in dairy cattle. It remains one of the most common reasons for the extensive use of antimicrobials in dairy farms leading to the emergence of antimicrobial-resistant pathogens. The aim of this study was to determine the patterns of antimicrobial resistance of Escherichia coli isolates from bovine mastitis and to identify prominent antimicrobial resistance and virulence genes among isolated strains. Materials and Methods: Antimicrobial susceptibility testing against six antibiotic groups, including tetracyclines, aminoglycosides, beta-lactams, macrolides, sulfonamides, and fluoroquinolones was performed using the disk diffusion method. PCR was performed on resistant isolates to detect resistance and virulence genes using commercially available primers. Results: Out of 216 milk samples cultured, 14 samples yielded E. coli isolates. All isolates (100%) were resistant to ampicillin, amoxicillin, procaine penicillin, streptomycin, oxytetracycline, and sulfamethoxazole-trimethoprim. Only one isolate (7%) was sensitive to gentamicin, and all isolates (100%) were sensitive to enrofloxacin and ciprofloxacin. All isolates carried at least one resistance gene against one or more of the major antibiotic groups. All isolates carried the ereA, tetG, tetE, and tetB genes, followed by tetA (93%), ampC (86%), strA (86%), sul1 (78%), tetD (71%), tetC (57%), aadA (57%), and strB (36%). The lowest percentage of isolates carried bla1 (17%) and bla2 (12%) genes, and none of the isolates carried the qnrA gene. Most of the isolates (93%) carried the Shiga toxin 1 virulence gene, followed by complement resistance protein (79%), intimin (64%), Shiga toxin 2 (36%), cytotoxic necrotizing factor (35%), aerotaxis receptor (21%), and type 1 fimbriae (15%). Conclusion: Results of this study indicate that the high percentages of E. coli isolate from bovine mastitis are resistant to two or more of the major antibiotic groups, irrespective of the presence or absence of relevant resistance or virulence genes.
Proximity‐Coupling‐Induced Significant Enhancement of Coercive Field and Curie Temperature in 2D van der Waals Heterostructures

Magnetism in 2D has long been the focus of condensed matter physics due to its important applications in spintronic devices. A particularly promising aspect of 2D magnetism is the ability to fabricate 2D heterostructures with engineered optical, electrical, and quantum properties. Recently, the discovery of intrinsic ferromagnetisms in atomic thick materials has provided a new platform for investigations of fundamental magnetic physics. In contrast to 2D CrI3 and Cr2Ge2Te6 insulators, itinerant ferromagnetic Fe3GeTe2 (FGT), which has a larger intrinsic perpendicular anisotropy, higher Curie temperature (TC), and relatively better stability, is a promising candidate for achieving permanent room‐temperature ferromagnetism through interface or component engineering. Here, it is shown that the ferromagnetic properties of FGT thin flakes can be modulated through coupling with a FePS3. The magneto‐optical Kerr effect results show that the TC of FGT is improved by more than 30 K and that the coercive field is increased by ≈100% due to the proximity coupling effect, which changes the spin textures of FGT at the interface. This work reveals that antiferromagnet/ferromagnet coupling is a promising way to engineer the magnetic properties of itinerant 2D ferromagnets, which paves the way for applications in advanced magnetic spintronic and memory devices.
Phosphorylation of the glycine transporter 1

The extracellular levels of the neurotransmitter glycine in the brain are tightly regulated by the high-affinity glycine transporter 1 (GlyT1) and the clearance of glycine depends on its rate of transport and the levels of cell surface GlyT1. Over the past years, it has been shown that PKC activation diminishes the activity and promoted phosphorylation of several neurotransmitter transporters including the dopamine, serotonin and norepinephrine transporters however, its role is unknown for the glycine transporter. To get insights into the role of PKC activation on GlyT1 regulation, we used three N-terminus GlyT1 isoforms stably expressed in porcine aortic endothelial (PAE) cells and assaying for [P]-orthophosphate metabolic labeling. We demonstrated that the isoforms GlyT1a, GlyT1b, and GlyT1c were constitutively phosphorylated, and that phosphorylation was dramatically enhanced, in a time-dependent fashion, after PKC activation by phorbol ester (PMA). The phosphorylation was PKC-dependent, since pre-incubation of the cells with bisindolylmaleimide I (BIM), a selective PKC inhibitor, abolished the phorbol ester-induced phosphorylation. Moreover, blotting of a purified GlyT1 fraction with specific antibodies to phosphorylated tyrosine residues did not yield any signal that could correspond to GlyT1 phosphorylation, suggesting that the phosphorylation occurs at serine and/or threonine residues. In addition, by using more specific inhibitors to the different PKC isoenzymes, we were able to determine the PKC isoenzyme(s) involved in downregulation of glycine uptake and GlyT1 phosphorylation. Specifically, we found that pre-incubation of the cells with the selective PKCα/β inhibitor Gö6976 completely abolished the effect of phorbol ester on uptake and phosphorylation. On the other hand, incubation with either selective PKCβ inhibitors (PKCβ inhibitor or LY333531) prevented the PKC-dependent phosphorylation of GlyT1 without affecting the downregulation triggered by PMA. Taken together, this data suggest
Plasma Endothelial Glycocalyx Components as a Potential Biomarker for Predicting the Development of Disseminated Intravascular Coagulation in Patients With Sepsis

Background: Sepsis coagulopathy or disseminated intravascular coagulation (DIC) mainly due to progressive endothelial disruption and damage. The glycocalyx is expressed on the endothelial cell surface and contributes to anti-thrombogenicity, anti-inflammatory, and regulates vascular permeability. We aimed to evaluate the clinical utility of plasma glycocalyx components as biomarkers in predicting the onset of DIC in sepsis. Materials and methods: This was a prospective observational study of 45 patients with sepsis (June to December 2018). Demographic, clinical (Acute Physiology, Age, Chronic Health Evaluation II [APACHE II], Sequential Organ Failure Assessment [SOFA]), and laboratory data from medical records were analyzed. Endothelial glycocalyx components (syndecan-1, heparan sulfate, hyaluronan) were measured using an ELISA kit. Results: Among the 45 patients (23, sepsis; 22, septic shock), plasma syndecan-1, heparan sulfate, and hyaluronan levels were higher in those with septic shock and were positively correlated with disease severity as determined by the APACHE II and SOFA scores and lactate levels. Receiver operating characteristic curve analysis revealed high sensitivity and specificity of syndecan-1 for predicting septic shock. Further, these levels were compared between patients with or without the development of DIC. Plasma syndecan-1 and hyaluronan levels were significantly elevated in patients with DIC compared to those in patients without DIC and were strongly associated with activated partial thromboplastin time, prothrombin time, and platelet counts. Area under the curve values for predicting DIC based on syndecan-1 and hyaluronan levels measurements were 0.774 and 0.740, respectively. Conclusions: Increased plasma syndecan-1 and hyaluronan levels may be indicators of disease severity and useful predictors for DIC development in sepsis.
High methionine diet in skeletal muscle remodeling: Epigenetic mechanism of homocysteine mediated growth retardation.

Epigenetic DNA methylation is crucial for gene-imprinting/off-printing ensuring epigenetic memory but generates copious homocysteine (Hcy) unequivocally. That is why during pregnancy mothers are recommended 'folic acid' to avoid birth-defects because of elevated Hcy levels (hyperhomocysteinemia; HHcy). Children born with HHcy have musculoskeletal abnormalities/growth retardation. We focus on gut-dysbiotic microbiome implication that instigates "1-carbon metabolism" and HHcy causing growth retardation along with muscle abnormalities. We test hypothesis whether high methionine diet (HMD, an amino acid high in red-meat) a substrate for Hcy can cause skeletal muscle and growth retardation and treatment with probiotics (PB) mitigate muscle dysfunction. We employed cystathionine beta synthase; CBS deficient mouse; CBS+/- fed with/without HMD and with/without a probiotic in drinking water for 16 weeks. Matrix metalloproteinase activity; a hallmark of remodeling was measured by zymography. Muscle functions were scored via electric stimulation. Our results suggest that compared to WT, CBS+/- mice exhibited reduced growth. MMP-2 activity was robust in CBS+/- and HMD effects were attenuated by PB intervention. Electrical stimulation magnitude was decreased in CBS+/- and CBS+/- treated with HMD. Interestingly; PB mitigated muscle growth retardation and atrophy. Collectively, results imply that individuals with mild/moderate HHcy seem more prone to skeletal muscle injury and its dysfunction.
Clinical Oncology Society of Australia: Position statement on cancer‐related malnutrition and sarcopenia

Abstract This position statement describes the recommendations of the Clinical Oncology Society of Australia (COSA) regarding management of cancer‐related malnutrition and sarcopenia. A multidisciplinary working group completed a review of the literature, focused on evidence‐based guidelines, systematic reviews and meta‐analyses, to develop recommendations for the position statement. National consultation of the position statement content was undertaken through COSA members. All people with cancer should be screened for malnutrition and sarcopenia in all health settings at diagnosis and as the clinical situation changes throughout treatment and recovery. People identified as “at risk” of malnutrition or with a high‐risk cancer diagnosis or treatment plan should have a comprehensive nutrition assessment; people identified as “at risk” of sarcopenia should have a comprehensive evaluation of muscle status using a combination of assessments for muscle mass, muscle strength and function. All people with cancer‐related malnutrition and sarcopenia should have access to the core components of treatment, including medical nutrition therapy, targeted exercise prescription and physical and psychological symptom management. Treatment for cancer‐related malnutrition and sarcopenia should be individualised, in collaboration with the multidisciplinary team (MDT), and tailored to meet needs at each stage of cancer treatment. Health services should ensure a broad range of health care professionals across the MDT have the skills and confidence to recognise malnutrition and sarcopenia to facilitate timely referrals and treatment. The position statement is expected to provide guidance at a national level to improve the multidisciplinary management of cancer‐related malnutrition and sarcopenia.
Enhanced Agrobacterium‐mediated transformation revealed attenuation of exogenous plasmid DNA installation in recipient bacteria by exonuclease VII and SbcCD

In DNA transfer via type IV secretion system (T4SS), relaxase enzyme releases linear ssDNA in donor cells and recircularizes in recipient cells. Using VirB/D4 T4SS, Agrobacterium cells can transfer an IncQ‐type plasmid depending on Mob relaxase and a model T‐DNA plasmid depending on VirD2 relaxase. Mobilization to Escherichia coli of the former plasmid is much more efficient than that of the latter, whereas an entirely reverse relationship is observed in transfer to yeast. These data suggest that either plasmid recircularization or conversion of ssDNA to dsDNA in the recipient bacterial cells is a rate‐limiting step of the transfer. In this study, we examined involvement of exonuclease genes in the plasmid acceptability. By the VirD2‐dependent T‐DNA plasmid, E. coli sbcDΔ and sbcCΔ mutant strains produced threefold more exconjugants, and a sbcDΔ xseAΔ mutant strain yielded eightfold more exconjugants than their wild‐type strain. In contrast to the enhancing effect on the VirD2‐mediated transfer, the mutations exhibited a subtle effect on the Mob‐mediated transfer. These results support our working hypothesis that VirD2 can transport its substrate ssDNA efficiently to recipient cells and that recipient nucleases degrade the ssDNA because VirD2 has some defect(s) in the circularization and completion of complementary DNA synthesis.
Exosomal MicroRNA Expression Profiling Analysis of the Effects of Lycium Barbarum Polysaccharide on Gestational Diabetes Mellitus Mice

Objective Gestational diabetes mellitus (GDM) is a pathological condition, affecting an increasing number of pregnant women worldwide. Safe and effective treatment for GDM is very important for the public health. In this study, we utilized a high-fat diet-induced GDM model to evaluate the effects of LBP on GDM and examined the changes of exosomal microRNA expression profiling to decipher the potential underlying mechanism of LBP. Methods Female C57BL/6J mice were fed a control diet, HFD, or 150 mg/kg LBP-supplemented HFD for 6 weeks before conception and throughout gestation. Oral glucose tolerance test and plasma lipid levels were determined, and liver histopathology was assessed. Sequencing was used to define the microRNA expression profiling of plasma exosomes in the three groups of mice, and protein expression levels of the candidate target genes were analyzed. Results LBP significantly relieved glucose intolerance, abnormal plasma lipid levels, and pathomorphological changes of liver histopathology in HFD-induced GDM mice. Moreover, we found that this effect of LBP was mediated by downregulation of the increase of 6 miRNAs (miR-93-3p, miR-188-5p, miR-466k, miR-1188-5p, miR-7001-3p, and miR-7115-5p) and reversing the increase of the protein expression of CPT1A, which is the target gene of miR-188-5p. Conclusions Our findings provide novel insights into the biological activities of LBP in the treatment of GDM.