Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO) for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga) match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with appropriate instrumentation

Transformed non‐Hodgkin lymphoma in the rituximab era: analysis of the NCCN outcomes database

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100290/1/bjh12570.pd

Diffuse large B cell lymphoma presenting as a cardiac mass and odynophagia

Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We describe the case of a 77-year-old man who had initially been diagnosed with a left atrial mass on an echocardiogram, presenting with progressive dyspnea, dysphagia, odynophagia and fevers. The cardiac mass had been managed as an outpatient with full anticoagulation for the suspicion of clot. On admission, cardiac magnetic resonance imaging revealed a large mediastinal mass invading the left atrium that originated from the oesophagus. A barium oesophagram revealed an apple core lesion involving the distal third of the oesophagus. A subsequent computed tomography scan demonstrated a large mediastinal soft tissue mass and paratracheal lymphadenopathy. A flexible upper endoscopy revealed an oesophageal mass that was approximately 10 cm in length, irregular at the margins, and with a very necrotic appearance. This was biopsied, revealing findings consistent with high grade diffuse large B cell lymphoma. This case illustrates lymphoma presenting with dyspnea, odynophagia and a left atrial mass. To our knowledge, there are no reported cases of diffuse large B cell lymphoma presenting as odynophagia and a cardiac mass

Cardiac sarcoidosis and ventricular arrhythmias. A rare association of a rare disease. A retrospective cohort study from the National Inpatient Sample and current evidence for management

Background: Sarcoidosis is an increasingly recognized multi-systemic condition. Cardiac sarcoidosis is associated with ventricular arrhythmias and higher mortality rates. Little epidemiological data is available regarding the disease and associated ventricular arrhythmias. Methods: Data from the National Inpatient Sample (NIS) database 2012–2014, were reviewed. Dis­charges associated with sarcoidosis were identified as the target population using relevant ICD-9-CM codes. Primary outcome was a diagnosis of ventricular tachycardia (VT) in the sarcoidosis population. Secondary outcomes include rate of ventricular fibrillation (VF) and cardiac arrest. Subgroup analyses were performed to examine the association of VT with multiple potential confounding clinical variables. Results: Of 18,013,878 health encounters, 46,289 (0.26%) subjects had a diagnosis of sarcoidosis. VT and VF were more prevalent among patients with sarcoidosis compared to those without a diagnosis of sarcoidosis (2.29% vs. 1.22%; p < 0.001 and 0.25% vs. 0.21%; p < 0.001, respectively). Sarcoidosis was also associated with a higher prevalence of cardiac arrest (0.72% vs. 0.6%; p < 0.001). In unadjusted analyses, all examined comorbidities were significantly more common in those with sar­coidosis, including diabetes mellitus (31.6% vs. 21.25%; p < 0.001), hypertension (65.2% vs. 51.74%; p < 0.001), chronic kidney disease (21.09% vs. 14.02%; p < 0.001), heart failure (24.87% vs. 15%; p < 0.001) and acute coronary syndrome (4.32% vs. 3.35%; p < 0.001). Conclusions: The present study showed that sarcoidosis was associated with increased rates of ven­tricular tachyarrhythmia, which can affect the overall disease morbidity and mortality

Regulation of thymocyte positive selection and motility by GIT2

Thymocytes are highly motile cells that migrate under the influence of chemokines in distinct thymic compartments as they mature. The motility of thymocytes is tightly regulated; however, the molecular mechanisms that control thymocyte motility are not well understood. Here we report that G protein–coupled receptor kinase-interactor 2 (GIT2) was required for efficient positive selection. Notably, Git2−/− double-positive thymocytes showed greater activation of the small GTPase Rac, actin polymerization and migration toward the chemokines CXCL12 (SDF-1) and CCL25 in vitro. By two-photon laser-scanning microscopy, we found that the scanning activity of Git2−/− thymocytes was compromised in the thymic cortex, which suggests GIT2 has a key role in regulating the chemokine-mediated motility of double-positive thymocytes.National Institutes of Health (U.S.) (R01AI064227)Leukemia & Lymphoma Society of Americ

Patologiczna masa wewnątrzsercowa oraz odynofagia jako objawy rozlanego chłoniaka z dużych limfocytów B

Zajęcie mięśnia sercowego jako pierwsza manifestacja rozwijającego się chłoniaka złośliwego jest stosunkowo rzadkim zjawiskiem. W niniejszej pracy opisano przypadek kliniczny 77-letniego mężczyzny, u którego wstępnie na podstawie badania echokardiograficznego zdiagnozowano patologiczną masę w obrębie lewego przedsionka objawiającą się klinicznie pod postacią stopniowo narastającej duszności, dysfagii, odynofagii oraz gorączki. Patologiczna masa wewnątrzsercowa była wstępnie traktowana jako skrzeplina i jako taka była leczona w warunkach ambulatoryjnych za pomocą terapeutycznych dawek leków przeciwkrzepliwych. Przy przyjęciu wykonano rezonans magnetyczny, w którym wykazano duży patologiczny twór w obrębie śródpiersia, który swój początek miał w obrębie przełyku i naciekał lewy przedsionek. Rentgenowskie badanie kontrastowe przełyku z użyciem barytu uwidoczniło ubytek cienia o typowym wyglądzie ogryzka od jabłka, który obejmował dolną trzecią część przełyku. Na podstawie badania tomokomputerowego klatki piersiowej stwierdzono dużą patologiczną masę tkanek miękkich w obrębie śródpiersia z towarzyszącą limfadenopatią okołotchawiczą. W endoskopii wykonanej za pomocą giętkiego gastroskopu ujawniono obecność patologicznej masy w obrębie przełyku o długości około 10 cm, nieregularnych brzegach i silnie martwiczym wyglądzie makroskopowym. Wykonano biopsję opisanej powyżej zmiany oraz następcze badania histopatologiczne, na podstawie których rozpoznano rozlanego chłoniaka z dużych limfocytów B dużego stopnia. W niniejszej pracy przedstawiono przypadek kliniczny pacjenta z chłoniakiem objawiającym się dusznością, odynofagią i obecnością patologicznej masy w obrębie lewego przedsionka. Według autorów dotychczas nie opisano jeszcze takiego przypadku

The GIT–PIX complexes regulate the chemotactic response of rat basophilic leukaemia cells

Background information. Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. The GIT–PIX protein complexes are involved in the regulation of cell motility and adhesion and in the endocytic traffic of members of the family of G-protein-coupled receptors. We have investigated the function of the endogenous GIT complexes in the regulation of cell motility stimulated by fMLP (formyl-Met-Leu-Phe) peptide, in a rat basophilic leukaemia RBL-2H3 cell line stably expressing an HA (haemagglutinin)-tagged receptor for the fMLP peptide

Stretch-Induced Stress Fiber Remodeling and the Activations of JNK and ERK Depend on Mechanical Strain Rate, but Not FAK

BACKGROUND: Cells within tissues are subjected to mechanical forces caused by extracellular matrix deformation. Cells sense and dynamically respond to stretching of the matrix by reorienting their actin stress fibers and by activating intracellular signaling proteins, including focal adhesion kinase (FAK) and the mitogen-activated proteins kinases (MAPKs). Theoretical analyses predict that stress fibers can relax perturbations in tension depending on the rate of matrix strain. Thus, we hypothesized stress fiber organization and MAPK activities are altered to an extent dependent on stretch frequency. PRINCIPAL FINDINGS: Bovine aortic endothelial cells and human osteosarcoma cells expressing GFP-actin were cultured on elastic membranes and subjected to various patterns of stretch. Cyclic stretching resulted in strain rate-dependent increases in stress fiber alignment, cell retraction, and the phosphorylation of the MAPKs JNK, ERK and p38. Transient step changes in strain rate caused proportional transient changes in the levels of JNK and ERK phosphorylations without affecting stress fiber organization. Disrupting stress fiber contractile function with cytochalasin D or Y27632 decreased the levels of JNK and ERK phosphorylation. Previous studies indicate that FAK is required for stretch-induced cell alignment and MAPK activations. However, cyclic uniaxial stretching induced stress fiber alignment and the phosphorylation of JNK, ERK and p38 to comparable levels in FAK-null and FAK-expressing mouse embryonic fibroblasts. CONCLUSIONS: These results indicate that cyclic stretch-induced stress fiber alignment, cell retraction, and MAPK activations occur as a consequence of perturbations in fiber strain. These findings thus shed new light into the roles of stress fiber relaxation and reorganization in maintenance of tensional homeostasis in a dynamic mechanical environment