Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10.

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.

A Review of Design Strategies in SiO/C Composite Anodes for Rechargeable Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) are widely used in electric vehicles, portable electronic devices, clean energy storage, and other fields due to their long service life, high energy density, and low self-discharge rate, which also puts forward higher requirements for the performance of lithium-ion batteries. As an anode for lithium-ion batteries, SiO materials have garnered significant attention from researchers due to its high specific capacity (2400 mAh·g-1), abundance of raw materials, and simple preparation. However, its large volume change (~ 200%) and poor electrical conductivity hinder its large-scale commercial application. Researchers employ various methods to reduce the volume change of SiO during lithium intercalation and improve its structural stability during cycling. This work mainly reviews the chemical structure and lithium storage mechanism of SiO, as well as the latest research progress on the preparation methods of SiO/C anode materials, focusing on summarizing the following preparation strategies: chemical vapor deposition, mechanical ball milling, spray drying, and in-situ reduction/oxidation methods. The obtained SiO-based anode materials' structural characteristics and electrochemical properties are compared and summarized. Finally, this review discusses the advantages and disadvantages of the current preparation methods, the future research directions, and the development prospects of SiO-based anode materials.

Telomere C-Strand Fill-In Machinery: New Insights into the Human CST-DNA Polymerase Alpha-Primase Structures and Functions.

Telomeres at the end of eukaryotic chromosomes are extended by a specialized set of enzymes and telomere-associated proteins, collectively termed here the telomere "replisome." The telomere replisome acts on a unique replicon at each chromosomal end of the telomeres, the 3' DNA overhang. This telomere replication process is distinct from the replisome mechanism deployed to duplicate the human genome. The G-rich overhang is first extended before the complementary C-strand is filled in. This overhang is extended by telomerase, a specialized ribonucleoprotein and reverse transcriptase. The overhang extension process is terminated when telomerase is displaced by CTC1-STN1-TEN1 (CST), a single-stranded DNA-binding protein complex. CST then recruits DNA polymerase α-primase to complete the telomere replication process by filling in the complementary C-strand. In this chapter, the recent structure-function insights into the human telomere C-strand fill-in machinery (DNA polymerase α-primase and CST) will be discussed.

C-Peptide and BMi predict anti-hyperglycemic treatment lines in breast cancer patients treated with Alpelisib.

PURPOSE: Alpelisib is a PI3K (Phosphoinositide 3-kinases) inhibitor used for breast cancer which develops hyperglycemia based on its action on glucose metabolism regulation. This study aims to identify potential risk factors predicting hyperglycemia development and the need for multiple treatments for hyperglycemia in patients receiving Alpelisib. METHODS: Fourteen women diagnosed with metastatic hormone receptor-positive breast cancer carrying PI3K mutations who initiated treatment with Alpelisib were monitored through consultations in the Oncology and Endocrinology departments. Non-parametric ROC curves were generated to assess the need for three or more antidiabetic medications to achieve glycemic control. RESULTS: The study population had a median age of 64 years (range:48-69) with a median body mass index (BMI) of 26.6 kg/m2 (range: 22.9-29.4). Overweight was observed in 35.7% of the participants and obesity in 21.4%. Fifty percent of the participants had prediabetes, and 85.7% developed hyperglycemia requiring pharmacological treatment, although none of them needed to discontinue treatment for this reason. Baseline C-peptide levels and BMI were associated with the number of antidiabetic drugs used (Spearman's Rho 0.553, p = 0.040; Spearman's Rho 0.581, p = 0.030, respectively). ROC curve analysis showed and area under the curve (AUC) of 0.819 for the variable risk profile (defined as baseline C-peptide >10.5 ng/ml and BMI > 27 kg/m2), whereas AUC values were 0.556 and 0.514 for HbA1c and baseline glucose, respectively, (p = 0.012). CONCLUSION: A joint follow-up by an Oncology department and a Diabetes Unit can prevent treatment discontinuation in patients under Alpelisib therapy. Baseline BMI and plasma C-peptide levels can predict an increased need for anti-hyperglycemic treatment.

Scalp acupuncture guidance for identifying the optimal site for transcranial electrical stimulation of the hand.

Transcranial electrical stimulation (tES) often targets the EEG-guided C3/C4 area that may not accurately represent M1 for hand muscles. This study aimed to determine if the neuroanatomy-based scalp acupuncture-guided site (AC) was a more effective spot than the C3 site for neuromodulation. Fifteen healthy subjects received one 20-minute session of high-definition transcranial alternating current stimulation (HD-tACS) intervention (20 Hz at 2 mA) at the AC or C3 sites randomly with a 1-week washout period. Subjects performed ball-squeezing exercises with the dominant hand during the HD-tACS intervention. The AC site was indiscernible from the finger flexor hotspot detected by TMS. At the baseline, the MEP amplitude from finger flexors was greater with less variability at the AC site than at the C3 site. HD-tACS intervention at the AC site significantly increased the MEP amplitude. However, no significant changes were observed after tACS was applied to the C3 site. Our results provide evidence that HD-tACS at the AC site produces better neuromodulation effects on the flexor digitorum superficialis (FDS) muscle compared to the C3 site. The AC localization approach can be used for future tES studies.

Selective Oxidation of Vitamin D3 Enhanced by Long-Range Effects of a Substrate Channel Mutation in Cytochrome P450BM3 (CYP102A1).

Vitamin D deficiency affects nearly half the population, with many requiring or opting for supplements with vitamin D3(VD3), the precursor of vitamin D (1α,25-dihydroxyVD3). 25-HydroxyVD3, the circulating form of vitamin D, is a more effective supplement than VD3 but its synthesis is complex. We report here the engineering of cytochrome P450BM3(CYP102A1) for the selective oxidation of VD3 to 25-hydroxyVD3. Long-range effects of the substrate-channel mutation Glu435Ile promoted binding of the VD3 side chain close to the heme, enhancing VD3 oxidation activity that reached 6.62 g of 25-hydroxyVD3 isolated from a 1-litre scale reaction (69.1% yield; space-time-yield 331 mg/L/h).

Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus.

Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large 'cloud' of RNA genomes (quasispecies) which-by trial and error-comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.

Inhibition of microbially mediated total organic carbon decomposition in different types of cadmium contaminated soils with wheat straw addition.

Wheat straw returning is a common agronomic measure in the farmland. Understanding organic carbon transformation is of great significance for carbon budget under the premise of widespread distribution of cadmium (Cd) contaminated soils. An incubation experiment was conducted to assess the influence of Cd contamination on the decomposition and accumulation of total organic carbon (TOC) as well as the composition and abundance of bacterial communities in eight soil types with wheat straw addition. The results showed that inhibition of Cd contamination on microbially mediated organic carbon decomposition was affected by soil types. The lower cumulative C mineralization and higher TOC content could be observed in the acidic soils relative to that in the alkaline soils. The content of Cd in soil exhibits different effects on the inhibition in decomposition of TOC. The high dosage level of Cd had stronger inhibitory impact due to its high toxicity. The decomposition of TOC was restricted by a reduction in soil bacterial abundance and weakening of bacterial activities. Redundancy analysis (RDA) indicated that Proteobacteria and Gemmatimonadetes were abundant in alkaline Cd-contaminated soils with wheat straw addition, while Bacteroidetes dominated cumulative C mineralization in acidic Cd-contamination soils. Moreover, the abundance of predicted functional bacteria indicated that high-dose Cd-contamination and acid environment all inhibited the decomposition of TOC. The present study suggested that pH played an important role on carbon dynamics in the Cd-contaminated soils with wheat straw addition.

Antimicrobial peptide 2K4L inhibits the inflammatory response in macrophages and Caenorhabditis elegans and protects against LPS-induced septic shock in mice.

2K4L is a rationally designed analog of the short α-helical peptide temporin-1CEc, a natural peptide isolated and purified from the skin secretions of the Chinese brown frog Rana chensinensis by substituting amino acid residues. 2K4L displayed improved and broad-spectrum antibacterial activity than temporin-1CEc in vitro. Here, the antibacterial and anti-inflammatory activities of 2K4L in macrophages, C. elegans and mice were investigated. The results demonstrated that 2K4L could enter THP-1 cells to kill a multidrug-resistant Acinetobacter baumannii strain (MRAB 0227) and a sensitive A. baumannii strain (AB 22933), as well as reduce proinflammatory responses induced by MRAB 0227 by inhibiting NF-κB signaling pathway. Similarly, 2K4L exhibited strong bactericidal activity against A. baumannii uptake into C. elegans, extending the lifespan and healthspan of the nematodes. Meanwhile, 2K4L alleviated the oxidative stress response by inhibiting the expression of core genes in the p38 MAPK/PMK-1 signaling pathway and downregulating the phosphorylation level of p38, thereby protecting the nematodes from damage by A. baumannii. Finally, in an LPS-induced septic model, 2K4L enhanced the survival of septic mice and decreased the production of proinflammatory cytokines by inhibiting the signaling protein expression of the MAPK and NF-κB signaling pathways and protecting LPS-induced septic mice from a lethal inflammatory response. In conclusion, 2K4L ameliorated LPS-induced inflammation both in vitro and in vivo.

Research on the influencing factors of promoting flipped classroom teaching based on the integrated UTAUT model and learning engagement theory.

With the rapid advancement of educational technology, the flipped classroom approach has garnered considerable attention owing to its potential for enhancing students' learning capabilities. This research delves into the flipped classroom teaching methodology, employing the Unified Theory of Acceptance and Use of Technology (UTAUT), learning engagement theory, and the 4C skills (comprising communication, collaboration, creativity, and critical thinking) to investigate its effects on learning capabilities. The research surveyed 413 students from three universities in Jiangxi Province, employing stratified random sampling. SPSS 24.0 and Amos were used for structural equation modeling and hypothesis testing analysis. The findings indicate that: (1) Performance expectancy, effort expectancy, and peer influence significantly enhance students' learning engagement in the flipped classroom. (2) Students' learning engagement in the flipped classroom notably promotes their learning capabilities. (3) Performance expectancy, effort expectancy, and peer influence can significantly boost learning capabilities by increasing learning engagement. (4) Personality traits significantly moderate the effect of peer influence on learning engagement, highlighting the crucial role of individual differences in learning. (5) The level of students' learning engagement is differentially influenced by performance expectancy and peer influence across various academic disciplines. Ultimately, this research provides valuable insights for educational policymakers and guides improvements in teaching practices, collectively advancing educational quality and equity.

Phylogenomic analysis and dynamic evolution of chloroplast genomes of Clematis nannophylla.

Clematis nannophylla is a perennial shrub of Clematis with ecological, ornamental, and medicinal value, distributed in the arid and semi-arid areas of northwest China. This study successfully determined the chloroplast (cp) genome of C. nannophylla, reconstructing a phylogenetic tree of Clematis. This cp genome is 159,801 bp in length and has a typical tetrad structure, including a large single-copy, a small single-copy, and a pair of reverse repeats (IRa and IRb). It contains 133 unique genes, including 89 protein-coding, 36 tRNA, and 8 rRNA genes. Additionally, 66 simple repeat sequences, 50 dispersed repeats, and 24 tandem repeats were found; many of the dispersed and tandem repeats were between 20-30 bp and 10-20 bp, respectively, and the abundant repeats were located in the large single copy region. The cp genome was relatively conserved, especially in the IR region, where no inversion or rearrangement was observed, further revealing that the coding regions were more conserved than the noncoding regions. Phylogenetic analysis showed that C. nannophylla is more closely related to C. fruticosa and C. songorica. Our analysis provides reference data for molecular marker development, phylogenetic analysis, population studies, and cp genome processes to better utilise C. nannophylla.

Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia.

BACKGROUND: Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals. METHODS: Three members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022. RESULTS: All cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis. CONCLUSIONS: Here, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy.

Impact of aquaporin-4 and CD11c + microglia in the development of ependymal cells in the aqueduct: inferences to hydrocephalus.

AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4-/- mice (KO) due to stenosis of Silvio's aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4-/- mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.

Roles of cMyBP-C phosphorylation on cardiac contractile dysfunction in db/db mice.

Type 2 diabetes mellitus (T2DM) is a metabolic disease and comorbidity associated with several conditions, including cardiac dysfunction leading to heart failure with preserved ejection fraction (HFpEF), in turn resulting in T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying the development of T2DM-CM are poorly understood. It is hypothesized that molecular alterations in myopathic genes induced by diabetes promote the development of HFpEF, whereas cardiac myosin inhibitors can rescue the resultant T2DM-mediated cardiomyopathy. To test this hypothesis, a Leptin receptor-deficient db/db homozygous (Lepr db/db) mouse model was used to define the pathogenesis of T2DM-CM. Echocardiographic studies at 4 and 6 months revealed that Lepr db/db hearts started developing cardiac dysfunction by four months, and left ventricular hypertrophy with diastolic dysfunction was evident at 6 months. RNA-seq data analysis, followed by functional enrichment, revealed the differential regulation of genes related to cardiac dysfunction in Lepr db/db heart tissues. Strikingly, the level of cardiac myosin binding protein-C phosphorylation was significantly increased in Lepr db/db mouse hearts. Finally, using isolated skinned papillary muscles and freshly isolated cardiomyocytes, CAMZYOS ® (mavacamten, MYK-461), a prescription heart medicine used for symptomatic obstructive hypertrophic cardiomyopathy treatment, was tested for its ability to rescue T2DM-CM. Compared with controls, MYK-461 significantly reduced force generation in papillary muscle fibers and cardiomyocyte contractility in the db/db group. This line of evidence shows that 1) T2DM-CM is associated with hyperphosphorylation of cardiac myosin binding protein-C and 2) MYK-461 significantly lessened disease progression in vitro, suggesting its promise as a treatment for HFpEF.

Adaptive natural killer cell expression in response to cytomegalovirus infection in blood and solid cancer.

Natural Killer (NK) cells are conventionally thought to be an indefinite part of innate immunity. However, in a specific subset of NK cells, recent data signify an extension of their "duties" in immune surveillance and response, having characteristics of adaptive immunity, in terms of persistence and cytotoxicity. These cells are known as the adaptive or memory-like NK cells, where human cytomegalovirus (HCMV) infection has been shown to drive the expansion of adaptive NKG2C+ NK cells. HCMV is a ubiquitous pathogen whose prevalence differs worldwide with respect to the socioeconomic status of countries. The adaptive NK cell subpopulation is often characterized by the upregulated expression of NKG2C, CD16, and CD2, and restricted expression of NKG2A, FCεRγ and killer immunoglobulin-like receptors (KIR), although these phenotypes may differ in different disease groups. The reconfiguration of these receptor distributions has been linked to epigenetic factors. Hence, this review attempts to appraise literature reporting markers associated with adaptive or memory-like NK cells post-HCMV infection, in relation to solid cancers and hematological malignancies. Adaptive NK cells, isolated and subjected to ex vivo modifications, have the potential to enhance anti-tumor response which can be a promising strategy for adoptive immunotherapy.

Immunogenicity of PvCyRPA, PvCelTOS and Pvs25 chimeric recombinant protein of Plasmodium vivax in murine model.

In the Americas, P. vivax is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice's splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies.

Transcriptome analysis reveals the molecular mechanism of differences in growth between photoautotrophy and heterotrophy in Chlamydomonas reinhardtii.

Background: The green alga Chlamydomonas reinhardtii can grow photoautotrophically utilizing light and CO2, and heterotrophically utilizing acetate. The physiological and biochemical responses of autotrophy and heterotrophy are different in C. reinhardtii. However, there is no complete understanding of the molecular physiology between autotrophy and heterotrophy. Therefore, we performed biochemical, molecular and transcriptome analysis of C. reinhardtii between autotrophy and heterotrophy. Results: The cell growth characterization demonstrated that heterotrophic cell had enhanced growth rates, and autotrophic cell accumulated more chlorophyll. The transcriptome data showed that a total of 2,970 differentially expressed genes (DEGs) were identified from photoautotrophy 12h (P12h) to heterotrophy 12h (H12h). The DEGs were involved in photosynthesis, the tricarboxylic acid cycle (TCA), pyruvate and oxidative phosphorylation metabolisms. Moreover, the results of qRT-PCR revealed that the relative expression levels of malate dehydrogenase (MDH), succinate dehydrogenase (SDH), ATP synthase (ATPase), and starch synthase (SSS) were increased significantly from P12h and H12h. The protein activity of NAD-malate dehydrogenase (NAD-MDH) and succinate dehydrogenase (SDH) were significantly higher in the H12h group. Conclusion: The above results indicated that the high growth rate observed in heterotrophic cell may be the effects of environmental or genetic regulation of photosynthesis. Therefore, the identification of novel candidate genes in heterotrophy will contribute to the development of microalga strains with higher growth capacity and better performance for biomass production.

Comparison of Glomerular Filtration Rate Equations in a Rural New Mexico Cohort: Results from the COMPASS Study.

Rationale and Objective: The NKF-ASN Task Force recommends accurate kidney function estimation avoiding biases through racial adjustments. We explored the use of multiple kidney function biomarkers and hence estimated glomerular filtration rate (eGFR) equations to improve kidney function calculations in an ethnically diverse patient population. Study design: Prospective community cohort study. Setting and Participants: rural New Mexico clinic with patients > 18 yo. Methods: Markers of kidney function, IDMS-Creatinine (SCr), chemiluminescence Beta-2 Microglobulin (B2M), Nephelometry-calibrated ELISA Cystatin C (CysC), inflammation, glucose tolerance, demographics, BUN/UACR from the baseline visit of the COMPASS cohort, were analyzed by Kernel-based Virtual Machine learning methods. Results: Among 205 participants, the mean age was 50.1, 62% were female, 54.1% Hispanic American and 30.2% Native American. Average kidney function biomarkers were: SCr 0.9 mg/dl, B2M 1.8 mg/L, and CysC 0.7 mg/dl. The highest agreement was observed between SCr and B2M-based eGFR equations [mean difference in eGFRs: (4.48 ml/min/1.73m2], and the lowest agreement between B2M and CysC-based eGFR equations (-24.75 ml/min/1.73m2). There was no pattern of association between the differences in eGFR measures and gender. In the continuous analyses, the absolute eGFR value (p<2 x 10-16) and serum albumin (p =6.4 x 10-5) predicted the difference between B2M- and SCr-based e-GFR. The absolute eGFR value (p<2 x 10-16) and age (p =7.6 x 10-5) predicted the difference between CysC- and SCr-based e-GFR. Limitations: Relatively small sample size, elevated inflammatory state in majority of study participants and no inulin excretion rate measurements. Conclusion: B2M should be strongly considered as a kidney function biomarker fulfilling the criteria for the NKF-ASN. B2M's eGFR equation does not need adjustment for gender or race and showed the highest agreement with SCr-based eGFR equations.