The soybean Phytoglobin1 (GmPgb1) is involved in water deficit responses through changes in ABA metabolism.

Soybean (Glycine max), a major grain crop worldwide, is susceptible to severe yield loss due to drought. Soybean plants over-expressing and downregulating the soybean Phytoblobin1 (GmPgb1) were evaluated for their ability to cope with polyethylene glycol (PEG)-induced water deficit. Sense transformation of GmPgb1, which was more expressed in shoot tissue relative to roots, increased overall plant performance and tolerance to water stress by attenuating the PEG depression of photosynthetic gas exchange parameters and chlorophyll content, as well as reducing leaf injury and promoting root growth. The higher plant relative water content, as a result of GmPgb1 over-expression, was associated with higher transcript levels of three aquaporins: GmTIP1;5 and GmTIP2;5 GmPIP2;9, known to confer water stress tolerance. Opposite results were observed in plants suppressing GmPgb1, which were highly susceptible to PEG-induced stress. Transcriptional and metabolic analyses revealed higher ABA synthesis in dehydrating leaves of plants over-expressing GmPgb1 relative to those suppressing the same gene. The latter plants exhibited a transcriptional induction of ABA catabolic enzymes and higher accumulation of the ABA catabolite dehydrophaseic acid (DPA). Administration of 8'-acetylene ABA, an ABA agonist resistant to the ABA catabolic activity, was sufficient to restore tolerance in the GmPgb1 down-regulating plants suggesting that regulation of ABA catabolism is as important as ABA synthesis in conferring PEG-induced water stress tolerance. Screening of natural soybean germplasm also revealed a rapid and transient increase in foliar GmPgb1 in tolerant plants relative to their susceptible counterparts, thus confirming the key role exercised by this gene during water stress.

Effect Modification by Sex of the Hemoglobin Concentration on Frailty Risk in Hospitalized Older Patients.

BACKGROUND: Hemoglobin concentration differs by sex, possibly affecting any association between hemoglobin and frailty. This study aimed to evaluate the potential interaction effect of hemoglobin and sex on frailty in Chinese older inpatients. METHODS: A cross-sectional study was conducted between February 2015 and November 2017 in a tertiary hospital. Frailty was defined by the Fried phenotype. Hemoglobin concentration was measured with a standard procedure. Covariates included demographics, clinical characteristics, and serum biomarkers. Logistic regression was applied to examine the association between hemoglobin concentration and frailty. The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) were used to evaluate the additive interaction. RESULTS: A total of 619 older inpatients [mean age 69.26±7.44 years; 334 men, 285 women] were included. The mean hemoglobin concentration was significantly lower in the elderly who were frail (11.9 g/L in frail versus 13.1g/L in non-frail; p<0.001). In the multivariable regression models, lower hemoglobin in patients was significantly associated with frailty (adjusted odds ratio (OR) = 2.51, 95% CI:1.37, 4.60). The stratified analyses indicated that lower hemoglobin was associated with frailty among older inpatients with different characteristics. Female inpatients with lower hemoglobin had the highest risk of frailty (adjusted OR=6.43, 95%: 2.38, 17.3); there were interactions between hemoglobin and sex on the development of frailty (RERI=4.30, 95% CI=-1.41, 10.01; AP=0.67, 95% CI=0.37, 0.97;SI=4.80, 95% CI=1.22, 18.84). CONCLUSIONS AND IMPLICATIONS: Our study provided evidence that sex and lower hemoglobin have an interaction effect on frailty; it is suggested that clinicians may consider sex-specific strategies for the elderly to conform the concept of precision medicine.

Diagnostic validity of optic nerve head colorimetric assessment and optical coherence tomography angiography in patients with glaucoma.

BACKGROUND/AIMS: The aim of this study was to assess the optic nerve head (ONH) and macular vessel density with optical coherence tomography angiography (OCT-A) and the ONH haemoglobin (ONH Hb) amount with Laguna ONhE program in open-angle glaucoma (OAG) patients. METHODS: In this prospective observational cross-sectional study, 67 OAG patients and 41 healthy age-sex frequency matched subjects were examined with OCT-A and retinal photos. The circumpapillary (wcpVD), optic nerve head (iVD) and macular (wmVD) capillary vessel density of OCT-A and ONH colorimetric assessment to determine the ONH Hb amount using the Laguna ONhE program were evaluated. RESULTS: Significant differences between normal subjects and glaucoma patients in the wcpVD (22.18±3.42 vs 16.03±2.89%; p<0.001), iVD (18.31±5.56 vs 12.52±4.67%; p<0.001), wmVD (15.60±2.34 vs 13.34±2.32%; p<0.001) and amount of ONH Hb (71.10±1.67 vs 68.86±2.46%; p<0.001) and in the papillary cup (68.14±5.25 vs 64.77±5.08%; p=0.001) were found. The Laguna ONhE glaucoma discriminant function (GDF) index had a negative value in the OAG patients and normal values in healthy subjects (-18.76±13.31 vs 7.98±14.09; p<0.001). The area under the receiver operating characteristic (ROC) curve (AUROC) for discriminating between healthy and glaucomatous eyes was highest for wcpVD (0.93; 95% CI 0.86 to 0.97, p<0.0001), followed by GDF (0.92; 95% CI 0.86 to 0.97, p<0.0001), iVD (0.79; 95% CI 0.70 to 0.86; p<0.0001) and ONH Hb (0.78; 95% CI 0.69 to 0.85, p<0.0001). Pair wise comparisons showed that the AUROC of wcpVD (0.93) was not significantly different than GDF (0.92) (p=0.855). CONCLUSION: Laguna ONhE program and OCT-A have similar diagnostic validity in open-angle glaucoma patients.

Hemopressin as a breakthrough for the cannabinoid field.

Hemopressin (PVNFKFLSH in rats, and PVNFKLLSH in humans and mice), a fragment derived from the α-chain of hemoglobin, was the first peptide described to have type 1 cannabinoid receptor activity. While hemopressin was shown to have inverse agonist/antagonistic activity, extended forms of hemopressin (i.e. RVD-hemopressin, also called pepcan-12) exhibit type 1 and type 2 cannabinoid receptor agonistic/allosteric activity, and recent studies suggest that they can activate intracellular mitochondrial cannabinoid receptors. Therefore, hemopressin and hemopressin-related peptides could have location-specific and biased pharmacological action, which would increase the possibilities for fine-tunning and broadening cannabinoid receptor signal transduction. Consistent with this, hemopressins were shown to play a role in a number of physiological processes including antinociceptive and anti-inflammatory activity, regulation of food intake, learning and memory. The shortest active hemopressin fragment, NFKF, delays the first seizure induced by pilocarpine, and prevents neurodegeneration in an experimental model of autoimmune encephalomyelitis. These functions of hemopressins could be due to engagement of both cannabinoid and non-cannabinoid receptor systems. Self-assembled nanofibrils of hemopressin have pH-sensitive switchable surface-active properties, and show potential as inflammation and cancer targeted drug-delivery systems. Upon disruption of the self-assembled hemopressin nanofibril emulsion, the intrinsic analgesic and anti-inflammatory properties of hemopressin could help bolster the therapeutic effect of anti-inflammatory or anti-cancer formulations. In this article, we briefly review the molecular and behavioral pharmacological properties of hemopressins, and summarize studies on the intricate and unique mode of generation and binding of these peptides to cannabinoid receptors. Thus, the review provides a window into the current status of hemopressins in expanding the repertoire of signaling and activity by the endocannabinoid system, in addition to their new potential for pharmaceutic formulations.

The Effects of Trabecular Bypass Surgery on Conventional Aqueous Outflow, Visualized by Hemoglobin Video Imaging.

PRECIS: Hemoglobin Video Imaging (HVI) provides a noninvasive method to quantify aqueous outflow (AO) perioperatively. Trabecular bypass surgery (TBS) is able to improve, and in some cases re-establish, conventional AO. PURPOSE: The purpose of this study was to use HVI to illustrate and quantify effects of TBS on AO through the episcleral venous system. DESIGN: This is a prospective observational cohort study. PARTICIPANTS: Patients were recruited from Sydney Eye Hospital, Australia. The study included 29 eyes from 25 patients, 15 with glaucoma and 14 normal controls. TBS (iStent Inject) was performed on 14 glaucomatous eyes (9 combined phacoemulsification/TBS and 5 standalone TBS). Cataract surgery alone was performed on the remaining eye from the glaucoma group and 2 eyes from the control group. METHODS: We used HVI, a novel clinic-based tool, to visualize and quantify AO perioperatively during routine follow-up to 6 months. Angiographic blood flow patterns were observed within prominent aqueous veins on the nasal and temporal ocular surface. Aqueous column cross-section area (AqCA) was compared before and after surgery. MAIN OUTCOME MEASURES: AqCA, number of aqueous veins, intraocular pressure (IOP) before and after surgery, and number of IOP-lowering medications. RESULTS: Patients with glaucoma had reduced AqCA compared with normal controls (P=0.00001). TBS increased AqCA in 13 eyes at 1 month (n=14; P<0.002), suggesting improved AO. This effect was maintained at 6 months in 7 eyes (n=9, P≤0.05). All patients with unrecordable AO before surgery (n=3; 2 standalone TBS, 1 combined cataract/TBS) established measurable flow after TBS. IOP and/or medication burden became reduced in every patient undergoing TBS. Cataract surgery alone (n=3) increased AqCA in nasal and temporal vessels at 4 weeks after surgery. CONCLUSIONS: HVI provides a safe method for detecting and monitoring AO perioperatively in an outpatient setting. Improvement of AO into the episcleral venous system is expected after TBS and can be visualized with HVI. TBS is able to improve, and in some cases re-establish, conventional AO. Cataract surgery may augment this. Some aqueous veins were first seen after TBS and these patients had unstable postoperative IOP control, which possibly suggests reorganization of aqueous homeostatic mechanisms. HVI may confirm adequacy of surgery during short-term follow-up, but further work is required to assess the potential of HVI to predict surgical outcomes and assist with personalized treatment decisions.

Over-expression of the Zea mays phytoglobin (ZmPgb1.1) alleviates the effect of water stress through shoot-specific mechanisms.

Water deficit limits plant growth and development by interfering with several physiological and molecular processes both in root and shoot tissues. Through their ability to scavenge nitric oxide (NO), phytoglobins (Pgbs) exercise a protective role during several conditions of stress. While their action has been mainly documented in roots, it is unclear whether Pgb exercises a specific and direct role in shoot tissue. We used a Zea mays root-less system to assess how over-expression or down-regulation of ZmPgb1.1 influences the behavior of shoots exposed to polyethylene glycol (PEG)-simulated water deficit. Relative to their WT and ZmPgb1.1 down-regulating counterparts, PEG-treated shoots over-expressing ZmPgb1.1 exhibited a reduced accumulation of ROS and lipid peroxidation. These effects were ascribed to lower transcript levels of Respiratory Burst Oxidase Homolog (RBOH) genes encoding the ROS generating enzyme complex NADPH oxidase, and a more active antioxidant system. Furthermore, over-expression of ZmPgb1.1 attenuated the reduction in osmotic potential and relative water content experienced during water stress, an observation also demonstrated at a whole plant level, possibly through the retention of the expression of three aquaporins involved in water transfer and implicated in drought tolerance. Pharmacological treatments modulating NO and ethylene levels revealed that the ZmPgb1.1 action was mediated by ethylene synthesis and response, with NO acting as an upstream intermediate. Collectively we provide substantial evidence that ZmPgb1.1 exercises a direct role in shoot tissue, independent from that previously reported in roots, which confers tolerance to water stress.

The Nobel Mabel. The woman who discovered that low oxygen stimulates hemoglobin production.

The research of Mabel Purefoy FitzGerald (1872-1973) was recently recognized by Sir Peter Ratcliffe in his public lecture at the awarding of the Nobel Prize in Physiology or Medicine as a critical step in the recent delineation of the oxygen sensing pathway. This brief article offers a tantalizing glimpse into the life of a woman whose scientific career spanned four countries, worked with eminent scientists and clinicians including Haldane and Osler, and published important physiologic discoveries. Her accomplishments and astounding life were lost to history for more than one hundred years and it is time to bring her back. When this diminutive and proper English woman set out on her own to the wild and remote mining towns of Colorado, little did she know that this would be the moment for which she would be remembered in her long, productive research career and ludicrous struggle to become a physician more than a century ago. Hers is an extraordinary tale of privilege, hardship, discrimination, shocking perseverance, and grand adventure.

Longitudinal Training-related Hematological Changes in Boys and Girls from Ages 12 to 15 yr.

PURPOSE: Natural growth and maturation cause hemoglobin mass (Hbmass) and blood volume (BV) to increase during childhood and adolescence. Whether endurance training during the same period can cause further increases in these variables is not clear. Also, body composition develops differently in girls and boys during puberty, and the effect of these differences on hematological variables has not been previously studied. METHODS: Forty-two endurance athletes (End group; 24 boys) and 34 athletes from other sports (non-End group; 23 boys) were tested at ages 12, 13, and 15 yr for Hbmass, BV, plasma volume (PV), red cell volume (RCV), hematological variables, and anthropometrics. RESULTS: At age 12 yr, Hbmass and BV showed no difference between sexes and training groups in absolute values or relative to fat-free mass (FFM). Relative to FFM, Hbmass and BV averaged 11.7 (0.8) g·kg and 95 (6.8) mL·kg. Increases in FFM from ages 12 to 15 yr primarily determined the increased Hbmass and BV for both sexes with no differences between training groups. At age 15 yr, Hbmass relative to FFM was higher in boys than girls, 13.1 (0.8) g·kg and 12.1 (0.9) g·kg (P < 0.001), whereas BV relative to FFM was not significantly different between sexes and training groups at any ages, averaged 100 (6.7) mL·kg at age 15 yr. Relative to FFM, PV was higher in the End group at all ages, and RCV was, on average, lower and increased less compared with non-End group. CONCLUSION: Our results indicate that increases in Hbmass during puberty are mainly associated with increased FFM and independent of sex or volume of endurance training.However, the FFM-relative PV was higher and the FFM-relative RCV was lower in the End group compared with the non-End group.

Platelet activity with hemoglobin level in patients with hemodialysis: Prospective study.

BACKGROUND: VerifyNow (VN; Accumetrics, San Diego, CA) P2Y12 reaction unit (PRU) has an inverse relation with hemoglobin level (Hb). Chronic kidney disease (CKD) is associated with low response to clopidogrel and low Hb. Our aim is to investigate the relation between PRU and Hb, and to assess whether Hb directly affects PRU or not in patients with CKD undergoing hemodialysis (HD). METHODS: We analyzed the relation between PRU and Hb in 43 HD patients and compared it with a control group of 127 patients with normal renal function. Both groups underwent percutaneous coronary intervention for stable coronary artery disease. We also compared PRU between the 2 groups considering Hb as a confounding factor. RESULTS: In the control group, Hb and PRU showed a significant inverse correlation (correlation coefficient r = -0.340; P < .001), but not in the HD group (correlation coefficient r = -0.099; P = .53). PRU was higher in the HD group than the control group after adjusting for the influence of Hb (299.2 [95% confidence interval: 278.4-316.7] vs 248.7 [95% confidence interval: 227.7-269.0]; P < .001), even after propensity score matching (299.2 [95% confidence interval: 278.4-316.7] vs 241.7 [95% confidence interval: 221.8-262.2]; P < .001). CONCLUSIONS: PRU was higher regardless of lower Hb in CKD on HD patients than normal renal function patients. Therefore, Hb was not crucial factor to decide PRU in CKD on HD patients in this study.

Associations of Hemoglobin Levels With Health-Related Quality of Life, Physical Activity, and Clinical Outcomes in Persons With Stage 3-5 Nondialysis CKD.

OBJECTIVE: Conflicting findings and knowledge gaps exist regarding links between anemia, physical activity, health-related quality of life (HRQOL), chronic kidney disease (CKD) progression, and mortality in moderate-to-advanced CKD. Using the CKD Outcomes and Practice Patterns Study, we report associations of hemoglobin (Hgb) with HRQOL and physical activity, and associations of Hgb and physical activity with CKD progression and mortality in stage 3-5 nondialysis (ND)-CKD patients. DESIGN AND METHODS: Prospectively collected data were analyzed from 2,121 ND-CKD stage 3-5 patients, aged ≥18 years, at 43 nephrologist-run US and Brazil CKD Outcomes and Practice Patterns Study-participating clinics. Cross-sectional associations were assessed of Hgb levels with HRQOL and physical activity levels (from validated Kidney Disease Quality of Life Instrument and Rapid Assessment of Physical Activity surveys). CKD progression (first of ≥40% estimated glomerular filtration rate [eGFR] decline, eGFR<10 mL/min/1.73 m2, or end-stage kidney disease) and all-cause mortality with Hgb and physical activity levels were also evaluated. Linear, logistic, and Cox regression analyses were adjusted for country, demographics, smoking, eGFR, serum albumin, very high proteinuria, and 13 comorbidities. RESULTS: HRQOL was worse, with severe anemia (Hgb<10 g/dL), but also evident for mild/moderate anemia (Hgb 10-12 g/dL), relative to Hgb>12 g/dL. Odds of being highly physically active were substantially greater at Hgb>10.5 g/dL. Lower Hgb was strongly associated with greater CKD progression and mortality, even after extensive adjustment. Physical inactivity was strongly associated with greater mortality and weakly associated with CKD progression. Possible residual confounding is a limitation. CONCLUSION: This multicenter international study provides real-world observational evidence for greater HRQOL, physical activity, lower CKD progression, and greater survival in ND-CKD patients with Hgb levels >12 g/dL, exceeding current treatment guideline recommendations. These findings help inform future studies aimed at understanding the impact of new anemia therapies and physical activity regimens on improving particular dimensions of ND-CKD patient well-being and clinical outcomes.

Hypoxia by Altitude and Welfare of Captive Beaded Lizards (Heloderma Horridum) in Mexico: Hematological Approaches.

Heloderma horridum is one of the few known venomous lizards in the world. Their populations are in decline due to habitat destruction and capture for the pet trade. In México, many zoos have decided to take care of this species, most of them at altitudes greater than the natural altitudinal distribution. However, we know little about the capacity of the reptiles to face high-altitude environments. The objective of this study was to compare hematological traits of H. horridum in captivity in high and low altitude environments. Our findings show that H. horridum does not respond to hypoxic environments, at least in blood traits, and that the organisms appear to be in homeostasis. Although we cannot know if individual H. horridum housed in high-altitude environments are completely comfortable, it appears hypoxia can be avoid without modifications of blood parameters. We suggest that future work should address changes in metabolic rates and in behavioral aspects to understand how to maintain the health and comfort of the reptiles native to low altitude when they are housed in high-altitude environments.

Effects of Ramadan fasting on athletes' hematological indices: a systematic review.

OBJECTIVE: To evaluate the effects of Ramadan fasting on hematological data in athletes through a systematic appraisal of the literature. DESIGN: Systematic review Data sources: The entire content of two databases, PubMed/MEDLINE and Web of Science Eligibility criteria for selecting studies: Ramadanrelated measurements of any hematological indices in athletes were considered. Both single-group pre-post with and without a control group studies conducted in athletes and published in English language before December 31, 2018 were included. Study appraisal: The methodological quality of the studies identified was assessed using 'QualSyst'. RESULTS: Of nine selected articles, eight were of moderate quality and only one was of strong quality. The main problem to date has been a lack of appropriate controls. Compared to before Ramadan, hematocrit and hemoglobin values increased in three studies, decreased in one study and did not change in one study during Ramadan fasting. Another study reported increased hematocrit and a puzzling decrease of hemoglobin during as compared to before Ramadan fasting. In most studies, blood platelet counts and the limited number of immune function used to date remainedunchanged. CONCLUSIONS: All reported changes in hematological indices remained within the normal reference range of the laboratory. Therefore, regular training can continue safely during Ramadan fasting from a hematological view point.

Involvement of hemoglobins in the pathophysiology of Alzheimer's disease.

Hemoglobins (Hbs) are heme-containing proteins binding oxygen, carbon monoxide, and nitric oxide. While erythrocytes are the most well-known location of Hbs, Hbs also exist in neurons, glia and oligodendroglia and they are primarily localized in the inner mitochondrial membrane of neurons with likely roles in cellular respiration and buffering protons. Recently, studies have suggested links between hypoxia and neurodegenerative disorders such as Alzheimer Disease (AD) and furthermore suggested involvement of Hbs in the pathogenesis of AD. While cellular immunohistochemical studies on AD brains have observed reduced levels of Hb in the cytoplasm of pre-tangle and tangle-bearing neurons, other studies on homogenates of AD brain samples observed increased Hb levels. This potential discrepancy may result from differential presence and function of intracellular versus extracellular Hbs. Intracellular Hbs may protect neurons against hypoxia and hyperoxia. On the other hand, extracellular free Hb and its degradation products may trigger inflammatory immune and oxidative reactions against neural macromolecules and/or damage the blood-brain barrier. Therefore, biological processes leading to reduction of Hb transcription (including clinically silent Hb mutations) may influence intra-erythrocytic and neural Hbs, and reduce the transport of oxygen, carbon monoxide and nitric oxide which may be involved in the (patho)physiology of neurodegenerative disorders such as AD. Agents such as erythropoietin, which stimulate both erythropoiesis, reduce eryptosis and induce intracellular neural Hbs may exert multiple beneficial effects on the onset and course of AD. Thus, evidence accumulates for a role of Hbs in the central nervous system while Hbs deserve more attention as possible candidate molecules involved in AD.

Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and Introgression.

A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance. Experiments revealed that the introgressed coding variants confer an increased Hb-O2 affinity in conjunction with an enhanced Bohr effect. We also document that affinity-enhancing mutations in the ß-globin gene of Tibetan wolf were originally derived via interparalog gene conversion from a tandemly linked ß-globin pseudogene. Thus, affinity-enhancing mutations were introduced into the ß-globin gene of Tibetan wolf via one form of intragenomic lateral transfer (ectopic gene conversion) and were subsequently introduced into the Tibetan mastiff genome via a second form of lateral transfer (introgression). Site-directed mutagenesis experiments revealed that the increased Hb-O2 affinity requires a specific two-site combination of amino acid replacements, suggesting that the molecular underpinnings of Hb adaptation in Tibetan mastiff (involving mutations that arose in a nonexpressed gene and which originally fixed in Tibetan wolf) may be qualitatively distinct from functionally similar changes in protein function that could have evolved via sequential fixation of de novo mutations during the breed's relatively short duration of residency at high altitude.

Paediatric reference intervals are heterogeneous and differ considerably in the classification of healthy paediatric blood samples.

The aim was to elude differences in published paediatric reference intervals (RIs) and the implementations hereof in terms of classification of samples. Predicaments associated with transferring RIs published elsewhere are addressed. A local paediatric (aged 0 days to < 18 years) population of platelet count, haemoglobin level and white blood cell count, based on first draw samples from general practitioners was established. PubMed was used to identify studies with transferable RIs. The classification of local samples by the individual RIs was evaluated. Transference was done in accordance with the Clinical and Laboratory Standards Institute EP28-A3C guideline. Validation of transference was done using a quality demand based on biological variance. Twelve studies with a combined 28 RIs were transferred onto the local population, which was derived from 20,597 children. Studies varied considerably in methodology and results. In terms of classification, up to 63% of the samples would change classification from normal to diseased, depending on which RI was applied. When validating the transferred RIs, one RI was implementable in the local population. Conclusion: Published paediatric RIs are heterogeneous, making assessment of transferability problematic and resulting in marked differences in classification of paediatric samples, thereby potentially affecting diagnosis and treatment of children. What is Known: • Reference intervals (RIs) are fundamental for the interpretation of paediatric samples and thus correct diagnosis and treatment of the individual child. • Guidelines for the establishment of adult RIs exist, but there are no specific recommendations for establishing paediatric RIs, which is problematic, and laboratories often implement RIs published elsewhere as a consequence. What is New: • Paediatric RIs published in peer-reviewed scientific journals differ considerably in methodology applied for the establishment of the RI. • The RIs show marked divergence in the classification of local samples from healthy children.

Characterization of the hemodynamic response function in white matter tracts for event-related fMRI.

Accurate estimates of the BOLD hemodynamic response function (HRF) are crucial for the interpretation and analysis of event-related functional MRI data. To date, however, there have been no comprehensive measurements of the HRF in white matter (WM) despite increasing evidence that BOLD signals in WM change after a stimulus. We performed an event-related cognitive task (Stroop color-word interference) to measure the HRF in selected human WM pathways. The task was chosen in order to produce robust, distributed centers of activity throughout the cortex. To measure the HRF in WM, fiber tracts were reconstructed between each pair of activated cortical areas. We observed clear task-specific HRFs with reduced magnitudes, delayed onsets and prolonged initial dips in WM tracts compared with activated grey matter, thus calling for significant changes to current standard models for accurately characterizing the HRFs in WM and for modifications of standard methods of analysis of functional imaging data.

In vivo hemodynamic visualization of berberine-induced effect on the cerebral cortex of a mouse by photoacoustic tomography.

While berberine, a traditional Oriental herbal drug commonly used for treatment of diarrhea, has recently been used to treat a number of brain disorders, such as stroke and Alzheimer's disease, berberine-induced changes in hemodynamics are largely unknown. Here, we utilize photoacoustic tomography (PAT) to study hemodynamic effects of berberine in mice. In vivo photoacoustic images are obtained in ten functional regions of a mouse brain. Cortical vascular network and dynamic changes in total hemoglobin (HbT) concentration are acquired at 532 nm. Functional atlas and statistical data are also obtained at low-dose and high-dose berberine. Our results provide compelling evidence that both low-dose and high-dose berberine can increase the HbT concentration to a varied extent in certain brain regions. This study also suggests that PAT provides a powerful tool for visualizing brain hemodynamic changes induced by drugs.

Comprehensive overview of hemoglobin mass and blood volume in elite athletes across a wide range of different sporting disciplines.

BACKGROUND: The aim of the study was to compare total hemoglobin mass (tHb-mass) and blood volume (BV) across elite athletes with different sporting specializations. METHODS: The study enrolled 222 members of Russian national teams from 12 different sporting disciplines and non-Olympic sports. The athletes were tested in the middle of a competitive season for tHb-mass, BV, plasma volume (PV), hemoglobin concentration (Hb), and hematocrit level (Hct) determination. tHb-mass measurements were performed using CO- rebreathing technique, alongside Hb and Hct (capillary blood). RESULTS: In elite endurance athletes both male and female values for tHb-mass, BV and PV, were significantly higher compared to anaerobic, technical sports and untrained subjects. The highest values of relative tHb-mass across all 15 groups were found in cross-country skiers (15.1±0.1 g/kg) and cyclists (15.0±0.5 g/kg). In the anaerobic group the highest value of tHb-mass was within the short-track group - i.e. 12.9±0.5 g/kg which was significantly lower than in cycling. In all aerobic groups, anaerobic and breath-hold divers we found significant difference in relative tHb-mass compared to untrained subjects. The difference between relative tHb-mass in the cycling group and untrained subjects was 31.3%, 17% for short track, 30.1% for handball and 33.5% for motor sport. For the largest group (biathlon) we performed correlation analysis for males and females with competitive performance and found relationship in both groups (P<0.05). CONCLUSIONS: The study clearly demonstrates the difference between endurance and non-endurance athletes in tHb-mass for elite males and females athletes and its importance in competitive aerobic performance.

In vitro differentiation of tracheary elements is induced by suppression of Arabidopsis phytoglobins.

Differentiation of tracheary elements (TEs) in vitro was affected by the expression level of the Arabidopsis thaliana Col-0 phytoglobins (Pgbs). Over-expression of Pgb1 or Pgb2 (35S:Pgb1 or 35S:Pgb2 lines) reduced the differentiation process while suppression of either Pgb (Pgb1-RNAi or pgb2 lines) enhanced the production of TEs. The inductive effect of Pgb suppression on TE differentiation was linked to the reduced expression of the transcription factor MYC2. Suppression of this gene, observed under conditions of high NO levels or low Pgb expression, was sufficient to promote TE differentiation, while its over-expression abolished the promotive effect of Pgb suppression on the differentiation process. Cells in which MYC2 was mutated accumulated ethylene which induced the expression of the homeodomain-leucine zipper (HD-Zip) III ATHB8. Production of ethylene was reduced in cells over-expressing MYC2 in a WT or a pgb mutant background. While stabilizing procambial cell specification, ATHB8 in known to activate downstream components triggering programmed cell death (PCD) and modifications of cell wall components, required steps of the TE differentiation process. Collectively, we provide evidence that in addition to their recognised participation in stress responses, Pgbs may play a key role in the specification of cell fate during development.