HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans

Hypoxia inducible factors, including HIF1A and HIF2A, play central roles in response to high-altitude hypoxia and genetic variants of HIF1A or HIF2A were associated with high-altitude sickness or adaptation. However, it remains to determine whether they are associated with tolerance to different levels of high-altitude selection pressure among native Tibetans. We recruited 189 Tibetan subjects living at 2,700 meters (Low level of high altitude, LHA), 197 at 3,200 meters (Middle level of high altitude of high altitude, MHA), 249 at 3,700 meters (High level of high altitude, HHA) and 269 at 4,700 meters (Very high level of high altitude, VHA) and performed association analysis of twelve tSNPs (tagging SNPs) in HIF1A and HIF2A with high-altitude. We found (1) a increasing trend of HIF2A rs5621780-C(18.4%, 15.9%, 32.8% and 31.1%, respectively, in LHA, MHA, HHA and VHA)(P = 3.56E-9); (2) increasing trends of HIF2A rs6756667-A(68.7%, 73.4%, 79.9% and 89.6%), rs7589621- G(74.6%, 77.9%, 83.7%, and 92.1%) and rs1868092-A(64.1%, 67.3%, 75.1% and 84.4%) (P = 3.56E-9, 4.68E-16, 1.17E-13 and 7.09E-14, respectively); (3) a increasing trend of haplotype AG (68.7%, 73.1%, 79.9% and 89.6%) (P = 2.22E-7) which was constructed by rs6756667 and rs7589621; (4) a strong linear correlation between major alleles of rs6756667-A (R ² = 0.997, P = 0.002), rs7589621-G (R ² = 0.994, P = 0.003), rs1868092-A (R ² = 0.985, P = 0.008) and altitude by linear correlation test. The associations between HIF2A variants and different level of high altitude support that extremely high-altitude hypoxia challenge imposes selective effects on HIF2A variants among native Tibetans.     

Motor Performance Assessment in Parkinson’s Disease: Association between Objective In-Clinic,Objective In-Home,and Subjective/Semi-Objective Measures

Advances in wearable technology allow for the objective assessment of motor performance in both in-home and in-clinic environments and were used to explore motor impairments in Parkinson’s disease (PD). The aims of this study were to: 1) assess differences between in-clinic and in-home gait speed, and sit-to-stand and stand-to-sit duration in PD patients (in comparison with healthy controls); and 2) determine the objective physical activity measures, including gait, postural balance, instrumented Timed-up-and-go (iTUG), and in-home spontaneous physical activity (SPA), with the highest correlation with subjective/semi-objective measures, including health survey, fall history (fallers vs. non-fallers), fear of falling, pain, Unified Parkinson''s Disease Rating Scale, and PD stage (Hoehn and Yahr). Objective assessments of motor performance were made by measuring physical activities in the same sample of PD patients (n = 15, Age: 71.2±6.3 years) and age-matched healthy controls (n = 35, Age: 71.9±3.8 years). The association between in-clinic and in-home parameters, and between objective parameters and subjective/semi-objective evaluations in the PD group was assessed using linear regression-analysis of variance models and reported as Pearson correlations (R). Both in-home SPA and in-clinic assessments demonstrated strong discriminatory power in detecting impaired motor function in PD. However, mean effect size (0.94±0.37) for in-home measures was smaller compared to in-clinic assessments (1.30±0.34) for parameters that were significantly different between PD and healthy groups. No significant correlation was observed between identical in-clinic and in-home parameters in the PD group (R = 0.10–0.25; p>0.40), while the healthy showed stronger correlation in gait speed, sit-to-stand duration, and stand-to-sit duration (R = 0.36–0.56; p<0.03). This suggests a better correlation between supervised and unsupervised motor function assessments in healthy controls compared to PD group. In the PD group, parameters related to velocity and range-of-motion of lower extremity within gait assessment (R = 0.58–0.84), and turning duration and velocity within iTUG test (R = 0.62–0.77) demonstrated strong correlations with PD stage (p<0.01).     

Treating Urban Wastewater: Nutrient Removal by Using Immobilized Green Algae in Batch Cultures

Essential roles of microalgae during the tertiary treatment of municipal wastewater have been proven. In order to avoid wash out of the biomass and also modify the quality of the treated wastewater; some techniques such as cell immobilization have been developed. To do so, in this study four samples from two species of microalgae (Chlorella vulgaris and Chlamydomonas sp.) were determined and confirmed by taxonomic identification. The samples were immobilized in calcium alginate beads. Within 10 days the amounts of nitrate (No₃^?-N) and orthophosphate (Po₄^3?-P) were measured to calculate the removal efficacy for each individual sample. Based on the standard methods, the amount of nitrate and orthophosphate were determined every 3 days within 10 days. The results indicate that immobilized microalgae are able to remove the nutrients and reduce the amount of nitrate and orthophosphate, significantly. Furthermore, the C. vulgaris (YG02) was the best species in this experience with 72% and 99% of reduction in the amount of nitrate and orthophosphate, respectively.     

QM study and conformational analysis of an isatin Schiff base as a potential cytotoxic agent

Isatin is an important compound from the biological aspect of view. It is an endogenous substance and moreover; various pharmacological activities have been reported for isatin and its derivatives. In-vitro cytotoxic effects of the prepared isatin Schiff bases toward HeLa, LS180 and Raji human cancer cell lines has been reported in our previous work. 3-(2-(4-nitrophenyl)hydrazono) indolin-2-one was found to be the most potent one among the studied compounds (IC₃₀?=?12.2 and 21.8 μM in HeLa and LS-180 cell lines, respectively). Obtained biological data could be well interpreted using docking binding energies toward vascular endothelial growth factor receptor (VEGFR-2); a key anticancer target being biologically investigated against various isatin derivatives. In the present work, quantum mechanical (QM) method including functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP) was used to estimate individual ligand-residue interaction energies for the docked 3-(2-(4-nitrophenyl)hydrazono) indolin-2-one into VEGFR-2 active site. Results were further interpreted via calculated polarization effects induced by individual amino acids of the receptor active site. A fairly good correlation could be found between polarization effects and estimated binding energies (R²?=?0.7227). Conformational analysis revealed that 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one might not necessarily interact with the VEGFR-2 active site in its minimum energy conformation.

Prevalence of cytomegalovirus infection and its role in total immunoglobulin pattern in Iranian patients with different subtypes of multiple sclerosis

Multiple sclerosis (MS) is the most common autoimmune disease characterized by multifocal areas of inflammatory demyelination within the central nervous system. Cytomegalovirus (CMV) has a complex pathobiology and in most cases is simply asymptomatic. There is some recent controversy over the role of CMV in the pathology of MS. The aim of this study was to evaluate active CMV infection and its effect on the humoral immunity in patients with MS. Serum, plasma, peripheral blood mononuclear cells (PBMCs), saliva and urine collected from MS patients (n=78) and healthy subjects (n=123) were screened for the presence of anti-CMV antibodies and CMV-DNA by nephelometric and PCR methods. Concentrations of total antibodies in MS subtypes were measured using both nephelometric and enzyme linked fluorescent assay (ELFA) techniques. The results extend the observation of an increased frequency of CMV-DNA in patients, in contrast with controls (p<0.001). Furthermore, systemic CMV infections were found in 25.5% of patients and only 3.2% of controls (p<0.001). There was significant difference in the titers of anti-CMV IgG and total IgE in patient and controls (P<0.001). These results support the hypothesis that CMV may contribute to MS thought to establish systemic infection process and induce immune response.     

Antimicrobial susceptibility profiles associated with bacterial meningitis among children: a referral hospital-based study in Iran

Bacterial meningitis continues to be associated with high morbidity and mortality rate worldwide, especially in the pediatric age group. This study was performed to identify the microbial etiologies of meningitis among 31 children, who were admitted in the Emergency Ward of a referral pediatric hospital in Iran. Culture identification showed that Streptococcus pneumoniae (12 subjects), Haemophilus influenzae (11 subjects) were the most common bacteria, followed by Escherichia coli (7 cases) and Neisseria meningitidis (only one case). Antibiotic susceptibility tests revealed that vancomycin had the best effect on S. pneumoniae in comparison with other antibiotics, whereas H. influenzae and E. coli were more susceptible to ceftriaxone, ceftazidime, and ceftizoxime than other antibiotics. In conclusion, despite the advances in antibiotic therapy and vaccine development, bacterial meningitis still is a health problem. S. pneumoniae, H. influenzae, and N. meningitidis are the main sources of bacterial meningitis, but other organisms such as E. coli should also be suspected, when a case is admitted to a referral pediatric hospital.     

Chemotactic behavior of Campylobacter spp. in function of different temperatures (37 °C and 42 °C)

The chemotactic behaviour of Campylobacter strains was determined in the presence of different amino acids at two temperatures (37 °C and 42 °C). Two strains of catalase positive (Campylobacter jejuni) and negative (Campylobacter sputurum) Campylobacter were isolated from river water in Tonekabon, Iran and identified by phenotyping and 16srRNA Gene sequencing methods. Chemotactic responses of the isolates were assessed toward a variety of amino acids viz., L-cystine, L-asparagine, L-histidine, L-aspartic acid, L-serine, L-phenylalanine, L-leucine and L-tryptophan by disc and capillary methods at two temperatures: 37 °C and 42 °C. C. jejuni showed positive chemotactic response towards L-cystine,L-tryptophan, L-phenylalanine, - L-leucine, L-asparagine and L-Serine at both, 37 °C and 42 °C however, it was greater at 37 °C. C. sputurum showed negative or weak response towards all of the amino acids. In addition, C. jejuni illustrated strong chemotactic response to L-asparagine follow by L-serine and weak chemotaxis response to L-phenylalanine and L-cysteine at 37 °C. Overall, C. jejuni showed relatively strong chemotactic response to some amino acids, likewise it was greater at 37 °C. Hence, the human body temperature (37 °C) in compared to avian body temperature (42 °C) probably promotes chemotactic response of C. jejuni, which it might be a reason for causing disease in human being compared to avian.     

Mutations in leaf starch metabolism modulate the diurnal root growth profiles of Arabidopsis thaliana

Roots of Arabidopsis thaliana exhibit stable diurnal growth profiles that are controlled by the circadian clock. Here we describe the effects of mutations in leaf starch metabolism on the diurnal root growth characteristics of Arabidopsis thaliana. High temporal and spatial resolution video imaging was performed to quantify the growth kinetics of Arabidopsis wild-type as well as pgm, sex1, mex1, dpe1 and dpe2 starch metabolism mutants grown in three different photoperiods. As a result, root growth patterns of all genotypes displayed characteristic modifications in their diurnal kinetics that were also affected by the photoperiod. To further investigate the role of starch derived substrate deficiency on root growth, the effect of 0.05% extracellular sucrose was studied in 12 h-12 h light-dark cycles.Key words: diurnal root growth kinetics, dpe1, dpe2, mex1, pgm, sex1, starch metabolism, video imagingRoot growth of Arabidopsis thaliana is highly rhythmic with respect to the time of the day.^1–3 In general, root growth rates increase at night while most of the light period is characterized by declining elongation rates. Since a slow oscillation in root growth rate with a periodicity of approximately 24 h persists in free running conditions it was demonstrated that the circadian clock mediates these daily fluctuations.¹ Root growth at night is fueled by the degradation of starch within the leaves. Thus, a correspondence between the time taken to degrade starch reserves and the length of the night is important to optimize growth in C-limiting conditions. Gibon et al. observed a strong correlation between the rate of starch degradation and the relative growth rate when Arabidopsis Col-0 was grown in a range of different photoperiods.⁴ Therefore, to avoid periods of C starvation at the end of the night the circadian clock was postulated to function as a timer that adjusts degradation of starch to the prevailing length of the night.^1,5Root growth strongly depends on the supply of sucrose from the leaves. To investigate the effects of substrate depletion on root elongation at night, 12-day-old seedlings of Col-0, pgm and sex1 growing in a 16 h photoperiod were previously investigated by digital time resolved video imaging.¹ As a result, the diel growth response was strongly modified in pgm and sex1 as compared to the wild-type. Both mutants showed a pronounced inhibition of growth during the night and a gradual recovery of growth during the light period. To substantiate these findings, we here report on the root elongation patterns of additional mutants in starch metabolism, e.g., mex1, dpe1 and dpe2 detected at different photoperiods and elevated external sucrose supply.     

Lymphopenia in COVID‐19: Therapeutic opportunities

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS‐CoV‐2, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.     

Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia

Blood flow restoration to ischemic tissue is affected by various risk factors. The aim of this study was to examine gender effects on arteriogenesis and angiogenesis in a mouse ischemic hindlimb model. C57BL/6J mice were subjected to unilateral hindlimb ischemia. Flow recovery was less and hindlimb use impairment was greater in females. No gender difference in vessel number was found at baseline, although 7 days postsurgery females had fewer α-smooth muscle actin-positive vessels in the midpoint of the adductor region. Females had higher hindlimb vascular resistance, were less responsive to vasodilators, and were more sensitive to vasoconstrictors postligation. Western blotting showed that females had higher baseline levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in the calf, while 7 days postligation males had higher levels of VEGF, eNOS, and phosphorylated vasodilator stimulated phosphoprotein. Females had less angiogenesis in a Matrigel plug assay and less endothelial cell proliferation in vitro. Females have impaired recovery of flow, a finding presumably caused by multiple factors including decreased collateral remodeling, less angiogenesis, impaired vasodilator response, and increased vasoconstrictor activity; our results also suggest the possibility that new collateral formation, from capillaries, is impaired in females.