Inhibition of nitrogenase by oxygen in marine cyanobacteria controls the global nitrogen and oxygen cycles

International audienceCyanobacterial N2-fixation supplies the vast majority of biologically accessible inorganic nitrogen to nutrient-poor aquatic ecosystems. The process, catalyzed by the heterodimeric protein complex, nitrogenase, is thought to predate that of oxygenic photosynthesis. Remarkably, while the enzyme plays such a critical role in Earth's biogeochemical cycles, the activity of nitrogenase in cyanobacteria is markedly inhibited in vivo at a post-translational level by the concentration of O2 in the contemporary atmosphere leading to metabolic and biogeochemical inefficiency in N2 fixation. We illustrate this crippling effect with data from Trichodesmium spp. an important contributor of "new nitrogen" to the world's subtropical and tropical oceans. The enzymatic inefficiency of nitrogenase imposes a major elemental taxation on diazotrophic cyanobacteria both in the costs of protein synthesis and for scarce trace elements, such as iron. This restriction has, in turn, led to a global limitation of fixed nitrogen in the contemporary oceans and provides a strong biological control on the upper bound of oxygen concentration in Earth's atmosphere

Contrasting effects of preexisting hyperglycemia and higher body size on hospital mortality in critically ill patients: a prospective cohort study

Background: Obesity and diabetes mellitus are well-defined risk factors for cardiovascular mortality. The impact of antecedent hyperglycemia and body size on mortality in critical ill patients in intensive care units (ICUs) may vary across their range of values. Therefore, we prospectively analyzed the relationship between in-hospital mortality and preexisting hyperglycemia and body size in critically ill ICU patients to understand how mortality varied among normal, overweight, and obese patients and those with low, intermediate, and high glycated hemoglobin (HbA1c) levels. Methods: Medical history, weight, height, physiologic variables, and HbA1c were obtained during the first 24 h for patients who were consecutively admitted to the high complexity ICU of Hospital de Clínicas de Porto Alegre, Brazil, from April to August 2011. The relationships between mortality and obesity and antecedent hyperglycemia were prospectively analyzed by cubic spline analysis and a Cox proportional hazards model. Results: The study comprised 199 patients. The overall hospital mortality rate was 43.2% during a median 16 (8–28) days of follow-up. There was a progressive risk of in-hospital mortality with higher HbA1c levels, with the relationship becoming significant at HbA1c >9.3% compared with lower levels (hazard ratio 1.74; 95% confidence interval with Bonferroni correction 1.49–2.80). In contrast, mean body mass index (BMI) was higher in survivors than in nonsurvivors (27.2 kg/m2 ± 7.3 vs. 24.7 kg/m2 ± 5.0 P = 0.031, respectively). Cubic spline analysis showed that these relationships differed nonlinearly through the spectrum of BMI values. In a Cox proportional hazards model adjusted for Acute Physiology and Chronic Health Evaluation II score and HbA1c, the risk of in-hospital mortality progressively decreased with increasing BMI (BMI <20 vs. 20–23.9 kg/m2, P = 0.032; BMI <20 vs. 24–34.9 kg/m2, P = 0.010; BMI <20 vs. ≥35 kg/m2, P = 0.032). Conclusions: Our findings suggest that significant hyperglycemia prior to ICU admission is a risk factor for in-hospital mortality. Conversely, increasing BMI may confer an advantageous effect against mortality in critical illness independently of previous glycemic control

Coronavirus infection (SARS-CoV-2) in obesity and diabetes comorbidities : is heat shock response determinant for the disease complications?

Chronic infammation is involved in the pathogenesis of several metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). With the recent worldwide outbreak of coronavirus disease (SARS-CoV-2), it has been observed that individuals with these metabolic diseases are more likely to develop complications, increasing the severity of the disease and a poorer outcome. Coronavirus infection leads to the activation of adaptive and innate immune responses, resulting in massive infammation (to so called cytokine storm), which in turn can lead to damage to various tissues, septic shock and multiple organ failure. Recent evidence suggests that the common link between metabolic diseases and SARS-CoV-2 is the infammatory response (chronic/low-grade for metabolic diseases and acute/intense in coronavirus infection). However, the ability of the infected individuals to resolve the infammation has not yet been explored. The heat shock response (HSR), an important anti-infammatory pathway, is reduced in patients with metabolic diseases and, consequently, may impair infammation resolution and control in patients with SARS-CoV-2, thus enabling its amplifcation and propagation through all tissues. Herein, we present a new hypothesis that aims to explain the increased severity of SARS-CoV-2 infection in people with metabolic diseases, and the possible benefts of HSR-inducing therapies to improve the infammatory profle in these patients

Keskiaikainen Rooma : bysanttilaisten ja vieraiden käsitykset Bysantista ja bysanttilaisuudesta (843–1204)

Tarkastelen maisterintutkielmassani sitä, kuinka bysanttilaiset ja latinalaiset mutta pienissä määrin myös muinaisitäslaavit ja arabit näkivät Bysantin, bysanttilaisuuden ja bysanttilaiset keskibysanttilaisella kaudella vuosina 843‒1204. Lisäksi tarkastelen bysanttilaisten kieltä ja erityisesti, oliko se aikalaisten mukaan kreikan vai ”rooman” kieli. Alkuperäislähteinäni käytän bysanttilaisia Leo VI:n Taktikaa, Konstantinos VII:n De administrando imperiota, Anna Komnenen Aleksiasta sekä joitakin hagiografioita, joista eräät ovat peräisin Symeon Metafrasteen Menologionista ja yksi pidempi on omistettu Pyhälle Neilos Rossanolaiselle. Lisäksi käytän läntisiä Liutprand Cremonalaisen kirjoituksia ja ristiretkikronikoita sekä muinaisitäslaavilaista Nestorin kronikkaa. Arabien näkökulmia olen tuonut ilmi tutkimuskirjallisuuden avulla. Tutkielmani liittyy etenkin Anthony Kaldelliksen tutkimukselliseen kontekstiin, joka pyrkii samaten tarkastelemaan Bysanttia ja bysanttilaisuutta korostaen niiden roomalaisuutta. Tuon työssäni selkeästi ilmi sen, että bysanttilainen johtava maallinen älymystö piti selvästi Bysanttia Roomana ja sen asukkaita roomalaisina, mikä johtui siitä, että Bysantti oli Rooman valtakunnan suora jatkumo. Arabit ajattelivat samaan tapaan, mutta sekä latinalaiset että muinaisitäslaavit pitivät Bysanttia Kreikkana ja bysanttilaisia kreikkalaisina, mikä johtui pääasiassa siellä käytetystä kielestä mutta myös sen maantieteellisestä sijainnista. Käyttämäni bysanttilaiset hagiografiat muodostavat oman bysanttilaisen johtavan eliitin kirjoituksista eroavan ryhmänsä, joka ei keskity maallisiin asioihin ja joka saattaa liittää kotimaan valtion sijaan kaupunkiin. Tutkielmani osoittaa, että bysanttilaiset olivat oman käsityksensä mukaan kansoista tärkein, mikä oli merkittävä osa heidän maailmankatsomustaan. Bysanttilainen identiteetti muodostui muun muassa kielen ja itäisen kristinuskon lisäksi vaatetuksesta. Bysanttilainen ja ulkomaalainen huomasi bysanttilaisen tämän vaatteiden perusteella. Bysanttilaiset myös selvästikin liittivät kansansa antiikin roomalaisiin ja esiintyivät heidän jälkeläisinään. Työssäni kerron myös, mitä kieltä bysanttilaiset mielestään puhuivat. Leo VI, Konstantinos VII sekä Neilos Rossanolaisen hagiografia kutsuvat latinaa roomalaisten kieleksi, mutta jälkimmäinen paljastaa myös kutsuvansa kreikan kieltä kreikaksi. Huomattavasti näiden kirjoittajien ja tekstien jälkeen kirjottanut Anna Komnene taas kutsuu kreikan kieltä sekä kreikaksi että väliin myös ”roomaksi.” Ulkopuolisista lähteistäni vain latinalainen Liutprand Cremonalainen kiinnittää huomiota Bysanttilaisten kieleen kutsuen sitä loogisesti kreikaksi ja omaa kieltään latinaksi

MRI-based early diagnosis : a diabetic Charcot spine case report

Background: Spinal neuroarthropathy (SNA), also known as Charcot spine, is an uncommon aggressive arthropathy, secondary to loss of proprioceptive and nociceptive feedback from the spine. A diagnosis of SNA is frequently delayed due to the scarcity of symptoms in its early stages, leading to significant neurological deterioration. Therefore, prompt suspicion of the disease is critical to providing better outcomes. This case assembles two rare characteristics of SNA: diabetic aetiology and a precocious time of diagnosis, and aims to highlight the magnetic resonance imaging (MRI) findings that allowed for the diagnosis. Case presentation: A 44-year-old woman, with long-term type 1 diabetes, presented with a two-month history of progressive lumbar pain, difficulty in maintaining an upright position, and discrete trunk forward-leaning. Diabetesrelated vasculopathy and nephropathy were already known, and laboratory test results did not show any new abnormalities. A lumbar MRI revealed extensive signal intensity changes of the L2 and L3 vertebral bodies associated with marginal areas of enhancement and the involvement of regions adjacent to interapophyseal articulations and spinous processes from L2–L3 to L5–S1, in association with degenerative changes of the thoracolumbar spine. These findings were identified by the radiologist as suggestive of SNA. To rule out neoplastic and infectious disease, a bone biopsy at the L2–L3 level was executed. The pathology report revealed intervertebral disc material and fragments of fibrous tissue, with a complete absence of inflammatory cells. It was decided to perform a six-month MRI follow-up, which showed stability of the findings, confirming the hypothesis of Charcot spine. The patient was under clinical and radiological follow-up and did not require surgical fixation at the moment of diagnosis. After 2.5 years from the initial diagnosis, a new MRI revealed progression of the lesions with oedema and enlarged paravertebral soft tissues; these findings are compatible with the patient’s latest complaints of lumbar pain recurrence. Conclusion: To the best of our knowledge, this is the first case report of an MRI-based early diagnosis of diabetic SNA, a rare disease with nonspecific symptoms in its initial stages and a wide spectrum of differential diagnoses. The MRI findings, distinctly the involvement of both anterior and posterior spinal elements, were the key to allowing for the proper diagnosis. A precocious diagnosis, although challenging, is fundamental to providing early intervention and to preventing further neurological impairment

Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression

In vertebrates, the inner ear arises from the otic placode, a thickened swathe of ectoderm that invaginates to form the otic vesicle. We report that histone demethylase KDM4B is dynamically expressed during early stages of chick inner ear formation. A loss of KDM4B results in defective invagination and striking morphological changes in the otic epithelium, characterized by abnormal localization of adhesion and cytoskeletal molecules and reduced expression of several inner ear markers, including Dlx3. In vivo chromatin immunoprecipitation reveals direct and dynamic occupancy of KDM4B and its target, H3K9me3, at regulatory regions of the Dlx3 locus. Accordingly, coelectroporations of DLX3 or KDM4B encoding constructs, but not a catalytically dead mutant of KDM4B, rescue the ear invagination phenotype caused by KDM4B knockdown. Moreover, a loss of DLX3 phenocopies a loss of KDM4B. Collectively, our findings suggest that KDM4B play a critical role during inner ear invagination via modulating histone methylation of the direct target Dlx3

Effects of long term physical training upon the histochemistry and morphology of the ventral motor neurons

Thesis (Ph. D.)--Michigan State University. Department of Anatomy, 1968Includes bibliographical references (pages 77-88