Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.

Chronic kidney disease affects ~10% of people worldwide and there are no disease modifying therapeutics that address the underlying cause of any form of kidney disease. Genome wide association studies have identified the G1 and G2 variants in the apolipoprotein L1 (APOL1) gene as major contributors to a subtype of proteinuric kidney disease now referred to as APOL1-mediated kidney disease (AMKD). We hypothesized that inhibition of APOL1 could have therapeutic potential for this genetically-defined form of kidney disease.

Isolation and Characterization of Phosphate Transporter 1 (PHT1) Gene Promoter and 5' Deletion Analysis of Transcriptional Regulation Regions under Phosphate Stress in Transgenic Tobacco.

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to persistent P deficiency by coordinating the expression of genes involved in the alleviation of stress. Promoters of phosphate transporter genes are a great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils.

Seroprevalence and associated risk factors of leptospirosis in bovine dairy farms in Telangana state, India.

The current cross-sectional study aimed to determine the seroprevalence of Leptospira infection in bovine dairy farms in the Telangana state of India, as well as the associated risk factors, in order to implement effective preventive measures for disease control. A total of 469 blood samples were collected from 67 herds/farms in different areas, covering 20 administrative districts in the state. These samples consisted of 253 from cattle and 216 from buffaloes.

Effects of Supplementation of a Mycotoxin Mitigation Feed Additive in Lactating Dairy Cows Fed Mycotoxin-Contaminated Diet for an Extended Period.

mycotoxins are inactivated by rumen flora; however, a certain amount can pass the rumen and reticulum or be converted into biological active metabolites. Limited scientific evidence is available on the impact and mitigation of mycotoxins on dairy cows' performance and health, particularly when cows are exposed for an extended period (more than 2 months). The available information related to these mycotoxin effects on milk cheese-making parameters is also very poor.

Is Location Everything? Regulation of the Endothelial CCM Signaling Complex.

Recent advances have steadily increased the number of proteins and pathways known to be involved in the development of cerebral cavernous malformation (CCM). Our ability to synthesize this information into a cohesive and accurate signaling model is limited, however, by significant gaps in our knowledge of how the core CCM proteins, whose loss of function drives development of CCM, are regulated. Here, we review what is known about the regulation of the three core CCM proteins, the scaffolds KRIT1, CCM2, and CCM3, with an emphasis on binding interactions and subcellular location, which frequently control scaffolding protein function.

Factors Influencing Antibiotic Prescribing Behavior and Understanding of Antimicrobial Resistance Among Veterinarians in Assam, India.

This study investigates factors influencing veterinarians' antibiotic prescribing behaviors and their understanding of antimicrobial resistance (AMR). The study used a telephone survey of 50 veterinarians conducted in five districts in Assam state, India. The survey sought information on the most prevalent animal diseases, veterinarians' awareness of potential preventive measures, including factors determining antimicrobial prescribing; the types of antimicrobials used for different health conditions in different species, and possible options to reduce antimicrobial use (AMU).

The Efficacy of a Smectite-Based Mycotoxin Binder in Reducing Aflatoxin B Toxicity on Performance, Health and Histopathology of Broiler Chickens.

The aim of the experiment was to investigate the efficacy of a smectite-based clay binder (Toxo-MX) in reducing the toxicological effects of aflatoxin B (AFB) in commercial broiler chickens. A total of 450 one-day old male broiler chickens were randomly allocated into three treatment groups with ten replicates of 15 birds each in a 42-day feeding experiment. The dietary treatments included a negative control (NC, a basal diet with no AFB and binder), a positive control (PC, a basal diet contaminated with 500 ppb of AFB) and a smectite-based mycotoxin binder(Toxo-MX, PC with smectite clay binder).

Contribution of protein-protein interactions to the endothelial-barrier-stabilizing function of KRIT1.

Krev-interaction trapped protein 1 (KRIT1) is an endothelial scaffold protein that promotes adherens junction (AJ) stability. The precise mechanism by which KRIT1 promotes barrier stabilization is unclear. We tested the ability of a panel of KRIT1 constructs containing mutations that inhibit Rap1 binding, ICAP1α binding, disrupt KRIT1's phosphotyrosine-binding (PTB) domain, or direct KRIT1 to the plasma membrane, either alone or in combination, to restore barrier function in KRIT1-deficient endothelial cells.

Delineation of genotype × environment interaction for identification of stable genotypes for tillering phase drought stress tolerance in sugarcane.

Sugarcane is a trans-seasonal long-duration crop and tillering phase (60-150 days) is the most sensitive phase for moisture stress, causing significant reduction in biomass accumulation. The study focussed to assess the Genotype × Environment Interaction (GEI) for tillering phase moisture stress and to identify the stable genotypes in sugarcane. The study dealt with 14 drought tolerant genotypes and two standards (Co 86032 and CoM 0265) which were evaluated in two plant and one ratoon trials at four locations in Maharashtra, India.

Protein kinase Cα regulates the nucleocytoplasmic shuttling of KRIT1.

KRIT1 is a scaffolding protein that regulates multiple molecular mechanisms, including cell-cell and cell-matrix adhesion, and redox homeostasis and signaling. However, rather little is known about how KRIT1 is itself regulated. KRIT1 is found in both the cytoplasm and the nucleus, yet the upstream signaling proteins and mechanisms that regulate KRIT1 nucleocytoplasmic shuttling are not well understood.

Microvascular Mimetics for the Study of Leukocyte-Endothelial Interactions.

Introduction: The pathophysiological increase in microvascular permeability plays a well-known role in the onset and progression of diseases like sepsis and atherosclerosis. However, how interactions between neutrophils and the endothelium alter vessel permeability is often debated.

Methods: In this study, we introduce a microfluidic, silicon-membrane enabled vascular mimetic (μSiM-MVM) for investigating the role of neutrophils in inflammation-associated microvascular permeability.

Caries Incidence Among Obese Adolescents: A 3-year Prospective Study.

Purpose: To determine the incidence of caries in a 3-year follow-up of obese adolescents.

Materials And Methods: Seven-hundred eighty five 13-year-old school children were selected randomly. Caries was recorded according to WHO criteria and body mass index was assessed in a medical evaluation.

Assessing interactions of binary mixtures of Penicillium mycotoxins (PMs) by using a bovine macrophage cell line (BoMacs).

Penicillium mycotoxins (PMs) are toxic contaminants commonly found as mixtures in animal feed. Therefore, it is important to investigate potential joint toxicity of PM mixtures. In the present study, we assessed the joint effect of binary combinations of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA) and penicillic acid (PA) using independent action (IA) and concentration addition (CA) concepts.

A C. elegans model of electronic cigarette use: Physiological effects of e-liquids in nematodes.

Background: Electronic cigarettes (e-cigs) have recently become very popular particularly among the younger generation. These nicotine delivery devices are viewed as a preferable alternative to more conventional forms of tobacco use and are thought to reduce the risk of chronic obstructive pulmonary disease, the third leading cause of death worldwide. However, there is very little data available on the consequences of e-cig use, though recently nicotine-independent inflammatory responses have been reported.

Untreated Gross Dental Malocclusion in Adolescents: Psychological Impact and Effect on Academic Performance in School.

Purpose: To evaluate the psychological impact and effect on academic performance of untreated gross dental malocclusion in adolescents.

Materials And Methods: A total of 366 (181 girls and 185 boys) adolescents with gross dental malocclusion were selected for the study group. A modified oral aesthetic subjective impact scale questionnaire was applied in face-to-face interviews.

Effect of Penicillium mycotoxins on the cytokine gene expression, reactive oxygen species production, and phagocytosis of bovine macrophage (BoMacs) function.

Bovine macrophages (BoMacs) were exposed to the following Penicillium mycotoxins (PM): citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA) and penicillic acid (PA). PM exposure at the concentration that inhibits proliferation by 25% (IC25) differentially for 24h altered the gene expression of various cytokines. OTA significantly induced IL-1α expression (p<0.

In vitro exposure of Penicillium mycotoxins with or without a modified yeast cell wall extract (mYCW) on bovine macrophages (BoMacs).

Penicillium mycotoxins (PMs) are contaminants that are frequently found in grain or crop-based silage for animal feed. Previously, we have characterized the potential immunotoxicity of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA), and penicillic acid (PA) by using a bovine macrophage cell line (BoMacs). In the present study, cell proliferation was used as a bioassay endpoint to evaluate the efficacy of a modified yeast cell wall extract (mYCW), for preventing PM toxicity under various in vitro conditions such as the following: pH (3, 5, 7), incubation time (1, 2, 4, 6 h), percentage of mYCW (0.

Association between Traumatic Dental Injury, Obesity, and Socioeconomic Status in 6- and 13-Year-Old Schoolchildren.

Obesity and poverty are independent risk factors in trauma-related morbidity in children as well as adolescents. The main objective of this study was to investigate the association between traumatic dental injury, obesity, and socioeconomic status in 6- and 13-year-old schoolchildren in Davangere city, Karnataka, India. Data were obtained from 1,550 schoolchildren.

Incidence of dental trauma among obese adolescents--a 3-year-prospective study.

Objectives: The main objective of the present investigation was to estimate the incidence of traumatic dental injuries (TDI), in particular crown fractures in a 3-year follow-up of obese adolescents.

Materials And Methods: Seven hundred and eighty-five 13-year-old school children were selected randomly. The crown fracture was classified according to Andreasen's criteria by visual examination without radiographs.

Prevalence and associated factors to developmental defects of enamel in primary and permanent dentition.

Background: The disturbances during enamel formation manifesting as Developmental Defects of Enamel (DDE) present important clinical significance since they are responsible for aesthetic problems, dental sensitivity and may act as predisposing factor for dental caries. The aim of the present study was to examine the prevalence of DDE and associated etiological factors.

Materials And Methods: A total of 1550 children was examined, using a mouth mirror and a CPI probe.

Relationship between severe-early childhood caries, salivary mutans streptococci, and lactobacilli in preschool children of low socioeconomic status in Bengaluru city.

Aim: To find out the relationship between severe-early childhood caries (s-ECC) and salivary counts of mutans streptococci (MS) and lactobacillus (LB) in preschool children of low socioeconomic status.

Materials And Methods: A cross-sectional study was designed among 50 children aged 2-5 years selected from five Anganwadi centers in Bengaluru city. Clinical examination was carried out and caries status was recorded using the World Health Organization (WHO) criteria.

Exposure to Penicillium mycotoxins alters gene expression of enzymes involved in the epigenetic regulation of bovine macrophages (BoMacs).

In this study, the modulation of key enzymes involved in epigenetic regulation was assessed in immortalized bovine macrophages (BoMacs) following in vitro exposure to the following Penicillium mycotoxins: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA), penicillic acid (PA), or a combination of one of the above with OTA at the concentration that inhibits BoMac proliferation by 25 % (IC25). Real-time PCR analysis of the genes coding DNA methyltransferases (DNMTs), histone demethylases (JMJD-3 and UTX), as well as the class-1 histone deacetylases (HDAC-1, -2, and -3) and histone acetylase (Bmi-1) was assessed following 6 h of mycotoxin exposure. A change in the expression of JMJD-3 as well as HDAC-3, MPA (p = 0.

Association between obesity, dental caries and socioeconomic status in 6- and 13-year-old school children.

Purpose: To investigate the association between dental caries, obesity and socioeconomic status (SES) in 6-and 13-yearold school children in Davangere city, Karnataka, India.

Materials And Methods: Data were obtained from a cohort of 1,550 children. Dental caries detection was performed according to the World Health Organization criteria and the medical evaluation assessed the body mass index (BMI).