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Understanding past and present aqueous activity on Mars is critical to constraining martian aqueous geochemistry and habitability, and to searching for life on Mars. Assemblages of minerals observed at or near the martian surface include phyllosilicates, sulfates, iron oxides/hydroxides, and chlorides, all of which are indicative of a complex history of aqueous activity and alteration in the martian past. Furthermore, features observed on parts of the martian surface suggest present-day activity of subsurface brines and at least transient liquid water. Terrestrial analogs for younger and colder (Hesperian–Amazonian) martian geologic and climatic conditions are available in the McMurdo Dry Valleys (MDV) of Antarctica and provide opportunities for improved understanding of more recent aqueous activity on Mars. Here, we study the VXE-6 intermittent brine pond site from Wright Valley in the MDV region and use coordinated spectroscopy, X-ray diffraction, and elemental analyses to characterize the mineralogy and chemistry of surface sediments that have evolved in response to aqueous activity at this site. We find that brine pond activity results in mineral assemblages akin to aqueous alteration products associated with younger sites on Mars. In particular, surficial chlorides, a transition layer of poorly crystalline aluminosilicates and iron oxides/hydroxides, and a deeper gypsum-rich interval within the upper 10 cm of sediment are closely related at this Antarctic brine pond site. Activity of the Antarctic brine pond and associated mineral formation presents a process analog for chemical alteration on the martian surface during episodes of transient liquid water activity during the late Hesperian and/or more recently. Our results provide a relevant example of how aqueous activity in a cold and dry Mars-like climate may explain the co-occurrence of chlorides, clays, iron oxides/hydroxides, and sulfates observed on Mars.

Background: Previous studies suggest that different metabotropic glutamate (mGlu) receptor subtypes are potential drug targets for the treatment of absence epilepsy. However, no information is available on mGlu3 receptors. Objective: To examine whether (i) abnormalities changes of mGlu3 receptor expression/signaling are found in the somatosensory cortex and thalamus of WAG/Rij rats developing spontaneous absence seizures; (ii) selective activation of mGlu3 receptors with LY2794193 affects the number and duration of spike-wave discharges (SWDs) in WAG/Rij rats; and (iii) a genetic variant of GRM3 (encoding the mGlu3 receptor) is associated with absence epilepsy. Methods: Animals: immunoblot analysis of mGlu3 receptors, GAT-1, GLAST, and GLT-1; real-time PCR analysis of mGlu3 mRNA levels; assessment of mGlu3 receptor signaling; EEG analysis of SWDs; assessment of depressive-like behavior. Humans: search for GRM3 and GRM5 missense variants in 196 patients with absence epilepsy or other IGE/GGE Idiopathic Generalized Epilepsy (IGE)/ Genetic Generalized Epilepsy (GGE) and 125,748 controls. Results: mGlu3 protein levels and mGlu3-mediated inhibition of cAMP formation were reduced in the thalamus and somatosensory cortex of pre-symptomatic (25-27 days old) and symptomatic (6-7 months old) WAG/Rij rats compared to age-matched controls. Treatment with LY2794193 (1 or 10 mg/kg, i.p.) reduced absence seizures and depressive-like behavior in WAG/Rij rats. LY2794193 also enhanced GAT1, GLAST, and GLT-1 protein levels in the thalamus and somatosensory cortex. GRM3 and GRM5 gene variants did not differ between epileptic patients and controls. Conclusions: We suggest that mGlu3 receptors modulate the activity of the cortico-thalamo-cortical circuit underlying SWDs and that selective mGlu3 receptor agonists are promising candidate drugs for absence epilepsy treatment.

Basophils are innate immune cells associated with type 2 immunity, allergic reactions, and host defense against parasite infections. In this study, we show that the transcription factor PLZF, which is known for its essential role in the function and development of several innate lymphocyte subsets, is also important for the myeloid-derived basophil lineage. PLZF-deficient mice had decreased numbers of basophil progenitors in the bone marrow and mature basophils in multiple peripheral tissues. Functionally, PLZF-deficient basophils were less responsive to IgE activation and produced reduced amounts of IL-4. The altered function of basophils resulted in a blunted Th2 T cell response to a protein allergen. Additionally, PLZF-deficient basophils had reduced expression of the IL-18 receptor, which impacted migration to lungs. PLZF, therefore, is a major player in controlling type 2 immune responses mediated not only by innate lymphocytes but also by myeloid-derived cells.

Anti-helminth responses require robust type 2 cytokine production that simultaneously promotes worm expulsion and initiates the resolution of helminth-induced wounds and hemorrhaging. However, how infection-induced changes in hematopoiesis contribute to these seemingly distinct processes remains unknown. Recent studies have suggested the existence of a hematopoietic progenitor with dual mast cell-erythrocyte potential. Nonetheless, whether and how these progenitors contribute to host protection during an active infection remains to be defined. Here, we employed single cell RNA-sequencing and identified that the metabolic enzyme, carbonic anhydrase (Car) 1 marks a predefined bone marrow-resident hematopoietic progenitor cell (HPC) population. Next, we generated a Car1-reporter mouse model and found that Car1-GFP positive progenitors represent bipotent mast cell/erythrocyte precursors. Finally, we show that Car1-expressing HPCs simultaneously support mast cell and erythrocyte responses during Trichinella spiralis infection. Collectively, these data suggest that mast cell/erythrocyte precursors are mobilized to promote type 2 cytokine responses and alleviate helminth-induced blood loss, developmentally linking these processes. Collectively, these studies reveal unappreciated hematopoietic events initiated by the host to combat helminth parasites and provide insight into the evolutionary pressure that may have shaped the developmental relationship between mast cells and erythrocytes., Author summary Helminth parasites infect approximately 2 billion people and represent a significant public health concern. Helminths undertake complex developmental life cycles through multiple organs and as a result cause substantial tissue damage. To combat this, mammals have evolved mechanisms to initiate balanced immune responses that promote inflammation needed to seclude parasites in granulomas, reduce parasitic burdens and mitigate the consequences of helminth-induced wounds. Despite their clinical importance, the mechanisms that regulate these events remain poorly defined. Here we have uncovered a unique progenitor cell that supports both proinflammatory mast cell responses and red blood cell development, thereby simultaneously initiating both of these host-protective responses. Collectively, these studies reveal unappreciated events initiated by the host to combat pathogens that infect billions of individuals worldwide.

It is well established that T helper type 2 (TH2) immune responses are necessary not only to provide protection against helminth parasites but also to promote the detrimental inflammation associated with allergies and asthma. Given the importance of type 2 immunity and inflammation, many studies have focused on better understanding the factors that regulate TH2 cell development and activation. As a result, significant progress has been made in understanding the signaling pathways and molecular events necessary to promote TH2 cell polarization. In addition to the adaptive compartment, emerging studies are better defining the innate immune pathways needed to promote TH2 cell responses. Given the recent and substantial growth of this field, the purpose of this review is to highlight recent studies defining the innate immune events that promote immunity to helminth parasites and allergic inflammation. Emerging studies have begun to elucidate the importance of cytokine alarmins such as thymic stromal lymphopoietin (TSLP), IL-25 (IL-17E), and IL-33 in promoting type 2 immunity and inflammation following helminth challenge or exposure to allergens. Specifically, recent reports have begun to define the complex cellular networks these alarmins activate and their contribution to type 2 immunity and inflammation. Our increased understanding of the pathways that regulate type 2 cytokine-mediated immunity and inflammation have revealed novel therapeutic targets to treat both helminth infections and allergic disease states.

Car enzyme inhibition prevents mast cell responses and inflammation following Trichinella spiralis infection or the induction of food allergy–like disease., Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine–mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2–associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy–like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell–mediated inflammation.

We analyzed the amino acid content of seven lunar regolith samples returned by the Apollo 16 and Apollo 17 missions and stored under NASA curation since collection using ultrahigh-performance liquid chromatography with fluorescence detection and time-of-flight mass spectrometry. Consistent with results from initial analyses shortly after collection in the 1970s, we observed amino acids at low concentrations in all of the curated samples, ranging from 0.2 parts-per-billion (ppb) to 42.7ppb in hot-water extracts and 14.5–651.1ppb in 6M HCl acid-vapor-hydrolyzed, hot-water extracts. Amino acids identified in the Apollo soil extracts include glycine, d- and l-alanine, d- and l-aspartic acid, d- and l-glutamic acid, d- and l-serine, l-threonine, and l-valine, all of which had previously been detected in lunar samples, as well as several compounds not previously identified in lunar regoliths: α-aminoisobutyric acid (AIB), d- and l-β-amino-n-butyric acid (β-ABA), dl-α-amino-n-butyric acid, γ-amino-n-butyric acid, β-alanine, and ε-amino-n-caproic acid. We observed an excess of the l enantiomer in most of the detected proteinogenic amino acids, but racemic alanine and racemic β-ABA were present in some samples.We also examined seven samples from Apollo 15, 16, and 17 that had been previously allocated to a non-curation laboratory, as well as two samples of terrestrial dunite from studies of lunar module engine exhaust that had been stored in the same laboratory. The amino acid content of these samples suggested that contamination had occurred during non-curatorial storage.We measured the compound-specific carbon isotopic ratios of glycine, β-alanine, and l-alanine in Apollo regolith sample 70011 and found values of −21‰ to −33‰. These values are consistent with those seen in terrestrial biology and, together with the enantiomeric compositions of the proteinogenic amino acids, suggest that terrestrial biological contamination is a primary source of the amino acids in these samples. However, the presence of the non-proteinogenic amino acids such as AIB and β-ABA suggests the possibility of some contribution from exogenous sources.We did not observe a correlation of amino acid content with proximity to the Apollo 17 lunar module, implying that lunar module exhaust was not a primary source of amino acid precursors. Solar-wind-implanted precursors such as HCN also appear to be at most a minor contributor, given a lack of correlation between amino acid content and soil maturity (as measured by Is/FeO ratio) and the differences between the δ13C values of the amino acids and the solar wind.

The Works of Ibn Wāḍiḥ al-Yaʿqūbī (3 vols.) contains a translation of the writings of Abū al-`Abbās al-Ya`qūbī, a Muslim polymath of the third/ninth century. The works include the History (Ta’rikh); the Geography (Kitab al-buldan); a new translation of his essay (Mushakalat al-nas) and a set of fragments.

The FATC domain of Tel1 is studied via introduction of substitution and truncation mutations. It is found to be required for localization to sites of DNA damage and is essential for phosphorylation of exogenous substrates but dispensable for the intrinsic kinase activity., Two large phosphatidylinositol 3-kinase–related protein kinases (PIKKs), ATM and ATR, play a central role in the DNA damage response pathway. PIKKs contain a highly conserved extreme C-terminus called the FRAP-ATM-TRRAP-C-terminal (FATC) domain. In budding yeast, ATM and ATR correspond to Tel1 and Mec1, respectively. In this study, we characterized functions of the FATC domain of Tel1 by introducing substitution or truncation mutations. One substitution mutation, termed tel1-21, and a truncation mutation, called tel1-ΔC, did not significantly affect the expression level. The tel1-21 mutation impaired the cellular response to DNA damage and conferred moderate telomere maintenance defect. In contrast, the tel1-ΔC mutation behaved like a null mutation, conferring defects in both DNA damage response and telomere maintenance. Tel1-21 protein localized to DNA ends as effectively as wild-type Tel1 protein, whereas Tel1-ΔC protein failed. Introduction of a hyperactive TEL1-hy mutation suppressed the tel1-21 mutation but not the tel1-ΔC mutation. In vitro analyses revealed that both Tel1-21 and Tel1-ΔC proteins undergo efficient autophosphorylation but exhibit decreased kinase activities toward the exogenous substrate protein, Rad53. Our results show that the FATC domain of Tel1 mediates localization to DNA ends and contributes to phosphorylation of target proteins.

Three masses of the Chelyabinsk meteorite have been studied with a wide range of analytical techniques to understand the mineralogical variation and thermal history of the Chelyabinsk parent body. The samples exhibit little to no postentry oxidation via Mossbauer and Raman spectroscopy indicating their fresh character, but despite the rapid collection and care of handling some low levels of terrestrial contamination did nonetheless result. Detailed studies show three distinct lithologies, indicative of a genomict breccia. A light-colored lithology is LL5 material that has experienced thermal metamorphism and subsequent shock at levels near S4. The second lithology is a shock-darkened LL5 material in which the darkening is caused by melt and metal-troilite veins along grain boundaries. The third lithology is an impact melt breccia that formed at high temperatures (~1600 °C), and it experienced rapid cooling and degassing of S2 gas. Portions of light and dark lithologies from Chel-101, and the impact melt breccias (Chel-102 and Chel-103) were prepared and analyzed for Rb-Sr, Sm-Nd, and Ar-Ar dating. When combined with results from other studies and chronometers, at least eight impact events (e.g., ~4.53 Ga, ~4.45 Ga, ~3.73 Ga, ~2.81 Ga, ~1.46 Ga, ~852 Ma, ~312 Ma, and ~27 Ma) are clearly identified for Chelyabinsk, indicating a complex history of impacts and heating events. Finally, noble gases yield young cosmic ray exposure ages, near 1 Ma. These young ages, together with the absence of measurable cosmogenic derived Sm and Cr, indicate that Chelyabinsk may have been derived from a recent breakup event on an NEO of LL chondrite composition.

Câhiliyye ve ilk Islâm donemi Arap toplumunda erkekler arasinda transseksuellik ya da efemineligin acikca bilinen ve yerlesmis bir sekilde mevcudiyetine dair onemli deliller vardir. Diger erkeklerden farkli olarak bu efemineler ya da muhanneslerin cinsel egilimlerinin olmadigi dusunulerek kadinlarla serbestce arkadaslik etmelerine izin verilmis ve bunlar siklikla evlenecek olanlar arasinda arabulucu veya daha az bir mesruiyete sahip olarak bir tur muhabbet tellalligi vazifesi gormuslerdi. Onlar Emeviler Doneminde Mekke ve ozellikle en unlu hânende ve sâzendeler arasinda sayildiklari Medine’de Arap Muziginin gelismesi hususunda da onemli rol oynamislardi. Devlet tarafindan donem donem bazi eziyetlere maruz kalmis olsalar da bunlar onlarin cinsel statulerinden degil- ki cok azi disinda onlar birer homoseksuel olarak addedilmiyorlardi- Toplumun ve ozellikle kadinlarin ahlâki degerlerine zarar verdikleri dusunulen muzisyenlik ve copcatanlik faaliyetlerinden kaynaklaniyordu. Ozellikle Halife Suleyman b. Abdulmelik donemindeki agir baskilar, muhanneslerin varliklarini degilse de muzik ve toplumdaki unlerini sonlandirmistir

The Works of Ibn Wāḍiḥ al-Yaʿqūbī (3 vols.) contains a translation of the writings of Abū al-`Abbās al-Ya`qūbī, a Muslim polymath of the third/ninth century. The works include the History (Ta’rikh); the Geography (Kitab al-buldan); a new translation of his essay (Mushakalat al-nas) and a set of fragments.

Carbonaceous matter on the surfaces of black pyroclastic beads, collected from Shorty crater during the Apollo 17 mission, represents the first identification of complex organic material associated with any lunar sample. We report the chemical, physical and isotopic properties of this organic matter that together support a pre-terrestrial origin. We suggest the most probable source is through the accretion of exogenous meteoritic kerogen from micrometeorite impacts into the lunar regolith. Abiotic organic matter has been continuously delivered to the surfaces of the terrestrial planets and their moons by accretion of asteroidal and cometary material. Determining the nature, distribution and evolution of such matter in the lunar regolith has important implications for understanding the prebiotic chemical inventory of the terrestrial planets.

We report the first observation of indigenous carbonaceous matter in the martian meteorite Yamato 000593. The carbonaceous phases are heterogeneously distributed within secondary iddingsite alteration veins and present in a range of morphologies including areas composed of carbon-rich spheroidal assemblages encased in multiple layers of iddingsite. We also observed microtubular features emanating from iddingsite veins penetrating into the host olivine comparable in shape to those interpreted to have formed by bioerosion in terrestrial basalts. Key Words: Meteorite—Yamato 000593—Mars—Carbon. Astrobiology 14, 170–181.

The Martian meteorite ALH84001 preserves evidence of interaction with aqueous fluids while on Mars in the form of microscopic carbonate disks. These carbonate disks are believed to have precipitated 3.9 Ga ago at beginning of the Noachian epoch on Mars during which both the oldest extant Martian surfaces were formed, and perhaps the earliest global oceans. Intimately associated within and throughout these carbonate disks are nanocrystal magnetites (Fe3O4) with unusual chemical and physical properties, whose origins have become the source of considerable debate. One group of hypotheses argues that these magnetites are the product of partial thermal decomposition of the host carbonate. Alternatively, the origins of mag- netite and carbonate may be unrelated; that is, from the perspective of the carbonate the magnetite is allochthonous. For example, the magnetites might have already been present in the aqueous fluids from which the carbonates were believed to have been deposited. We have sought to resolve between these hypotheses through the detailed characterized of the compo- sitional and structural relationships of the carbonate disks and associated magnetites with the orthopyroxene matrix in which they are embedded. Extensive use of focused ion beam milling techniques has been utilized for sample preparation. We then compared our observations with those from experimental thermal decomposition studies of sideritic carbonates under a range of plausible geological heating scenarios. We conclude that the vast majority of the nanocrystal magnetites present in the car- bonate disks could not have formed by any of the currently proposed thermal decomposition scenarios. Instead, we find there is considerable evidence in support of an alternative allochthonous origin for the magnetite unrelated to any shock or thermal processing of the carbonates.

The prominence of cultured slave women in early ‘Abbāsid Baghdad, as objects of sale, gift, infatuation, and scandal, is well known, not least from a famous monograph about them by al-Jāi. Less attention has been paid to a similar situation obtaining with regard to slave boys. Numerous anecdotes testify to this phenomenon, however, and a preliminary analysis of the available material suggests that the ‘traffic in boys’ developed in imitation of that in slave women, sometime after the public expression of homoerotic sentiment in general had come to be accepted. The parallelism is nevertheless imperfect, due to several complicating factors, including the possibility of eunuchs serving as an object of erotic attraction as well as lingering resonances of an earlier paternal rather than erotic stance adopted by gentlemen toward their valets.

The Dry Valleys of Antarctica are an excellent analog of the environment at the surface of Mars. Soil formation histories involving slow processes of sublimation and migration of water-soluble ions in polar desert environments are characteristic of both Mars and the Dry Valleys. At the present time, the environment in the Dry Valleys is probably the most similar to that in the mid-latitudes on Mars although similar conditions may be found in areas of the polar regions during their respective Mars summers. It is thought that Mars is currently in an interglacial period, and that subsurface water ice is sublimating poleward. Because the Mars sublimation zones seem to be the most similar to the Antarctic Dry Valleys, the Dry Valleys-type Mars climate is migrating towards the poles. Mars has likely undergone drastic obliquity changes, which means that the Dry Valleys analog to Mars may be valid for large parts of Mars, including the polar regions, at different times in geologic history. Dry Valleys soils contain traces of silicate alteration products and secondary salts much like those found in Mars meteorites. A martian origin for some of the meteorite secondary phases has been verified previously; it can be based on the presence of shock effects and other features which could not have formed after the rocks were ejected from Mars, or demonstrable modification of a feature by the passage of the meteorite through Earth's atmosphere (proving the feature to be pre-terrestrial). The martian weathering products provide critical information for deciphering the near-surface history of Mars. Definite martian secondary phases include Ca-carbonate, Ca-sulfate, and Mg-sulfate. These salts are also found in soils from the Dry Valleys of Antarctica. Results of earlier Wright Valley work are consistent with what is now known about Mars based on meteorite and orbital data. Results from recent and current Mars missions support this inference. Aqueous processes are active even in permanently frozen Antarctic Dry Valleys soils, and similar processes are probably also occurring on Mars today, especially at the mid-latitudes. Both weathering products and life in Dry Valleys soils are distributed heterogeneously. Such variations should be taken into account in future studies of martian soils and also in the search for possible life on Mars.

Martian Meteorite ALH84001 contains four unusual features which have been interpreted as possible signatures of relic biogenic activity. After six years of intense study by the world's scientific community, the current status of the biogenic hypothesis is reviewed and shown to still be valid. Furthermore additional features have been observed in two younger Martian meteorites. The strongest argument for possible evidence of biogenic activity within the ALH84001 meteorite is the presence of truncated hexa-octahedral magnetite crystals which are only known on Earth to be the products of biology.

Intracellular magnetite (Fe_3O_4) crystals produced by magnetotactic bacteria strain MV-1 are in the single-domain size range, and are chemically pure. We have previously suggested that they exhibit an unusual crystal habit described as truncated hexa-octahedral. Such a crystal morphology has not been demonstrated for any inorganic population of magnetite, nor would it be expected, given considerations of symmetry and free energy. By inference, this morphology is a physical signature of a biological origin. Here we report data from transmission electron microscope (TEM) tomography of such crystals isolated from magnetotactic bacteria, which confirm the unusual geometry, originally proposed from classical TEM tilt imaging.

Analyses both support and are in opposition to the hypothesis that the Martian meteorite ALH84001 contains evidence for possible biogenic activity on Mars. New observations in two additional Martian meteorites, Nakhla (1.3 Ga old) and Shergotty (300–165 Ma old) indicate possible biogenic features. Features in the three Martian meteorites compare favorably with the accepted criteria for terrestrial microfossils and evidence for early life on the Earth. There is strong evidence for the presence of indigenous reduced carbon, biogenic magnetite, and the low-temperature formation of carbonate globules. The morphological similarities between terrestrial microfossils, biofilms, and the features found in the three Martian meteorites are intriguing but have not been conclusively proven. Every investigation must recognize the possibility of terrestrial contamination of the meteorites, whether or not the meteorites are Martian. The search for evidence of ancient life in Martian meteorites has emphasized the difficulties confronting the scientific community with the respect to the positive identification of evidence of past biogenic activity.

Organic polymeric substances are a fundamental component of microbial biofilms. Microorganisms, especially bacteria, secrete extracellular polymeric substances (EPS) to form slime layers in which they reproduce. In the sedimentary environment, biofilms commonly contain the products of degraded bacteria as well as allochthonous and autochthonous mineral components. They are complex structures which serve as protection for the colonies of microorganisms living in them and also act as nutrient traps. Biofilms are almost ubiquitous wherever there is an interface and moisture (liquid/liquid, liquid/solid, liquid/gas, solid/gas). In sedimentary rocks they are commonly recognized as stromatolites. We also discuss the distinction between bacterial biofilms and prebiotic films. The EPS and cell components of the microbial biofilms contain many cation chelation sites which are implicated in the mineralization of the films. EPS, biofilms, and their related components thus have strong preservation potential in the rock record. Fossilized microbial polymeric substances (FPS) and biofilms appear to retain the same morphological characteristics as the unfossilized material and have been recognized in rock formations dating back to the Early Archaean (3.5 b.y.). We describe FPS and biofilms from hot spring, deep-sea, volcanic lake, and shallow marine/littoral environments ranging up to 3.5 b.y. in age. FPS and biofilms are more commonly observed than fossil bacteria themselves, especially in the older part of the terrestrial record. The widespread distribution of microbial biofilms and their great survival potential makes their fossilized remains a useful biomarker as a proxy for life with obvious application to the search for life in extraterrestrial materials.

— Samples from a suite of Shergotty—Nakhla—Chassigny (SNC) meteorites were analyzed for their O isotopic ratios by a modified version of the laser fluorination technique. Measured isotopic ratios (17O/16O and 18O/16O) from bulk samples of the Shergottites, EETA79001, Shergotty and Zagami; the Nakhlite Lafayette; and Chassigny are similar to those reported in the literature, as are those from olivine and pyroxene mineral separates from Lafayette. Iddingsite, a preterrestrial alteration product of Lafayette, was measured for the first time as a separate phase. Oxygen isotopic ratios increase with the percentage of iddingsite in a sample to a maximum δ18O of 14.4% for a ∼90% separate. Based on these measurements, end-member iddingsite has a δ18O of 15.6%, which places it among other 18O-enriched secondary phases (carbonate and silica) observed in SNC meteorites. The relatively large difference in δ18O between iddingsite and the olivine and pyroxene it replaces (∼11%) is typical of low-temperature alteration products. A range of crustal fluid δ18O values can be interpreted from the δ18O for end-member iddingsite, assuming isotopic equilibrium was achieved during low-temperature hydrous alteration (

Nuclei of hydrogen atoms located over a carbon-carbon double bond in the presence of a strong magnetic field experience a perturbed magnetic field caused primarily by the magnetic anisotropy of the π bond. However, the commonly used theoretical model for predicting the shielding effect of an alkene double bond on hydrogen nuclei is sometimes inconsistent with the observed proton NMR chemical shifts in structures that have covalently bonded hydrogens located over a carbon-carbon double bond. We have used the ab initio gauge including atomic orbital (GIAO) method to calculate isotropic shielding values and to determine the proton NMR shielding increments for a simple model system: methane held at various positions over ethene. These shielding increments calculated for one proton of methane have been mapped as a function of their position in Cartesian coordinates relative to the center of ethene. A mathematical function has been fit to this three-dimensional shielding increment surface at each of four distances from the face of the ethene molecule. Additionally, a single mathematical equation has been developed for predicting the shielding caused by the carbon-carbon double bond in ethene. In contrast to the traditionally employed shielding model, our results predict deshielding for protons within 3 A above the center of a carbon-carbon double bond, consistent with experimental observations in several molecular systems. The NMR shielding increments predicted by this equation are compared to observed shielding increments in some test alkenes.

Gretebeck, Randall J., Dale A. Schoeller, Rick A. Socki, Janis Davis-Street, Everett K. Gibson, Leslie O. Schulz, and Helen W. Lane. Adaptation of the doubly labeled water method for subjects consuming isotopically enriched water. J. Appl. Physiol. 82(2): 563–570, 1997.—The use of doubly labeled water (DLW) to measure energy expenditure is subject to error if the background abundance of the oxygen and hydrogen isotope tracers changes during the test period. This study evaluated the accuracy and precision of different methods by which such background isotope changes can be corrected, including a modified method that allows prediction of the baseline that would be achieved if subjects were to consume water from a given source indefinitely. Subjects in this study were eight women (4 test subjects and 4 control subjects) who consumed for 28 days water enriched to resemble drinking water aboard the United States space shuttle. Test subjects and control subjects were given a DLW dose on days 1 and 15, respectively. The change to an enriched water source produced a bias in expenditure calculations that exceeded 2.9 MJ/day (35%), relative to calculations from intake-balance. The proposed correction based on the predicted final abundance of18O and deuterium after equilibration to the new water source eliminated this bias, as did the traditional use of a control group. This new modified correction method is advantageous under field conditions when subject numbers are limited.

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Fresh fracture surfaces of the martian meteorite ALH84001 contain abundant polycyclic aromatic hydrocarbons (PAHs). These fresh fracture surfaces also display carbonate globules. Contamination studies suggest that the PAHs are indigenous to the meteorite. High-resolution scanning and transmission electron microscopy study of surface textures and internal structures of selected carbonate globules show that the globules contain fine-grained, secondary phases of single-domain magnetite and iron sulfides. The carbonate globules are similar in texture and size to some terrestrial bacterially induced carbonate precipitates. Although inorganic formation is possible, formation of the globules by biogenic processes could explain many of the observed features, including the PAHs. The PAHs, the carbonate globules, and their associated secondary mineral phases and textures could thus be fossil remains of a past martian biota.

Few studies have addressed the interaction between energy balance and lean body mass in healthy subjects during spaceflight or its simulations. We used doubly labeled water to measure total energy expenditure (TEE) in nine healthy adult men during two 7-day periods, once before and once during a 10-day head-down bed-rest period. Mean TEE was 21% less during than before bed rest; however, neither basal (BEE) nor resting (REE) energy expenditures changed, implying that the lesser TEE resulted from a reduction in physical activity. During the bed-rest period, energy intake was 563 +/- 280 kcal/day higher than TEE (P < 0.05) but body weight, fluid balance, BEE, and REE did not change relative to before bed rest. However, the small but statistically significant increase in body fat (0.44 +/- 0.67 kg, P < 0.05) during the bed-rest period suggests that body weight alone does not accurately reflect changes in energy balance during antiorthostatic bed rest.

Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the detrimental inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cell populations contribute to type 2 cytokine-mediated inflammation through their enhanced ability to develop into mast cells. Here we identify that carbonic anhydrase (Car) enzymes are upregulated in type 2-asscoaited progenitor cells and demonstrate that Car enzyme inhibition was sufficient to prevent murine mast cell development, type 2 cytokine-mediated inflammation and protective immunity to Trichinella spiralis. Moreover, we show that Car enzyme inhibition was also sufficient to prevent intestinal mast cell responses in a murine model of food allergy-like disease. Finally, we performed translational studies and demonstrated that Car enzymes can be targeted with an FDA-approved inhibitor to prevent human mast cell development. Collectively these studies identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that FDA-approved Car enzyme inhibitors may possess additional off-label therapeutic potential that can be employed to treat mast cell-mediated inflammation.

Neutropenia is a significant risk factor for life threatening invasive fungal infections (IFI). Neutrophils are well known as important innate cells that promote the direct eradication of fungal pathogens but whether they mediate antifungal defense beyond their role as effectors is unclear. Here we demonstrate that a pulmonary infection with the clinically relevant fungal pathogen Aspergillus fumigatus induces the diversification of specialized antifungal neutrophils that are required for antifungal CCR2+ monocyte-derived dendritic cell (mo-DC) function. Selective depletion of neutrophils resulted in global transcriptional alterations of the antifungal CCR2+ monocyte response, limited mo-DC differentiation, and diminished conidiacidal activity. Impaired mo-DC antifungal activity in neutropenic mice was accompanied by significant upregulation of carbonic anhydrase 4 (Car4) expression in CCR2+ monocyte precursors. Pharmacological inhibition of Car4 with the FDA-approved drug methazolamide (MZ) rescued the antifungal response of mo-DC and protected neutropenic mice from invasive apergillosis. Thus, beyond their role as effectors, antifungal neutrophils facilitate antifungal mo-DC functions by regulating Car4 activity. Moreover, our data provide proof-of-principle evidence for the importance of carbonic anhydrases in shaping innate cell differentiation as well as for the off-label therapeutic benefit of carbonic anhydrase inhibitors to boost antifungal immunity in susceptible patient populations.

PURPOSE: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. METHODS: Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. KEY FINDINGS: For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). SIGNIFICANCE: Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31.3 preferentially predispose to myoclonic seizures or absence seizures, respectively. Phenotype- genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes.

Background Despite considerable progress in our understanding of land plant phylogeny, several nodes in the green tree of life remain poorly resolved. Furthermore, the bulk of currently available data come from only a subset of major land plant clades. Here we examine early land plant evolution using complete plastome sequences including two previously unexamined and phylogenetically critical lineages. To better understand the evolution of land plants and their plastomes, we examined aligned nucleotide sequences, indels, gene and nucleotide composition, inversions, and gene order at the boundaries of the inverted repeats. Results We present the plastome sequences of Equisetum arvense, a horsetail, and of Isoetes flaccida, a heterosporous lycophyte. Phylogenetic analysis of aligned nucleotides from 49 plastome genes from 43 taxa supported monophyly for the following clades: embryophytes (land plants), lycophytes, monilophytes (leptosporangiate ferns + Angiopteris evecta + Psilotum nudum + Equisetum arvense), and seed plants. Resolution among the four monilophyte lineages remained moderate, although nucleotide analyses suggested that P. nudum and E. arvense form a clade sister to A. evecta + leptosporangiate ferns. Results from phylogenetic analyses of nucleotides were consistent with the distribution of plastome gene rearrangements and with analysis of sequence gaps resulting from insertions and deletions (indels). We found one new indel and an inversion of a block of genes that unites the monilophytes. Conclusions Monophyly of monilophytes has been disputed on the basis of morphological and fossil evidence. In the context of a broad sampling of land plant data we find several new pieces of evidence for monilophyte monophyly. Results from this study demonstrate resolution among the four monilophytes lineages, albeit with moderate support; we posit a clade consisting of Equisetaceae and Psilotaceae that is sister to the "true ferns," including Marattiaceae.

Background Tortula ruralis, a widely distributed species in the moss family Pottiaceae, is increasingly used as a model organism for the study of desiccation tolerance and mechanisms of cellular repair. In this paper, we present the chloroplast genome sequence of T. ruralis, only the second published chloroplast genome for a moss, and the first for a vegetatively desiccation-tolerant plant. Results The Tortula chloroplast genome is ~123,500 bp, and differs in a number of ways from that of Physcomitrella patens, the first published moss chloroplast genome. For example, Tortula lacks the ~71 kb inversion found in the large single copy region of the Physcomitrella genome and other members of the Funariales. Also, the Tortula chloroplast genome lacks petN, a gene found in all known land plant plastid genomes. In addition, an unusual case of nucleotide polymorphism was discovered. Conclusions Although the chloroplast genome of Tortula ruralis differs from that of the only other sequenced moss, Physcomitrella patens, we have yet to determine the biological significance of the differences. The polymorphisms we have uncovered in the sequencing of the genome offer a rare possibility (for mosses) of the generation of DNA markers for fine-level phylogenetic studies, or to investigate individual variation within populations

New data on martian meteorite 84001 as well as new experimental studies show that thermal or shock decomposition of carbonate, the leading alternative non-biologic explanation for the unusual nanophase magnetite found in this meteorite, cannot explain the chemistry of the actual martian magnetites. This leaves the biogenic explanation as the only remaining viable hypothesis for the origin of these unique magnetites. Additional data from two other martian meteorites show a suite of biomorphs which are nearly identical between meteorites recovered from two widely different terrestrial environments (Egyptian Nile bottomlands and Antarctic ice sheets). This similarity argues against terrestrial processes as the cause of these biomorphs and supports an origin on Mars for these features.

Recognition of the earliest morphological or chemical evidence of terrestrial life has proved to be challenging, as organic matter in ancient rocks is commonly fragmentary and difficult to distinguish from abiotically-produced materials (Schopf, 1993; Van Zuilen et al., 2002; Altermann & Kazmierczak, 2003; Cady et al., 2003; Brasier et al., 2002, 2004, 2005; Hofmann, 2004; Skrzypczak et al., 2004, 2005). Yet, the ability to identify remnants of earliest life is critical to our understanding of the timing of life's origin on earth, the nature of earliest terrestrial life, and recognition of potential remnants of microbial life that might occur in extraterrestrial materials. The search for earliest life on Earth now extends to early Archean organic remains; these tend to be very poorly preserved and considerably more difficult to interpret than the delicately permineralized microfossils known from many Proterozoic deposits. Thus, recent efforts have been directed toward finding biosignatures that can help distinguish fragmentary remnants of ancient microbes from either pseudofossils or abiotic organic materials that may have formed hydrothermally or in extraterrestrial processes (House et al., 2000; Boyce et al., 2001; Kudryavtsev et al., 2001; Schopf, 2002; Schopf et al., 2002, 2005a,b; Cady et al., 2003; Garc a-Ruiz et al., 2003; Hofmann, 2004; Brasier et al., 2005; Rushdi and Simoneit, 2005; Skrzypczak et al., 2005). An exciting area of biosignature research involves the developing technology of NanoSIMS. NanoSIMS is secondary ion mass spectrometry (SIMS) for ultrafine feature, elemental and isotopic analysis. Its resolution approaches 0.05 micrometers for element mapping, which is 10-50 times finer than that attainable with conventional SIMS or electron microprobes. Consequently, NanoSIMS has the potential to reveal previously unknown, chemical and structural characteristics of organic matter preserved in geologic materials. Robert et al. (2005) were the first to combine NanoSIMS element maps with optical microscopic imagery in an effort to develop a new method for assessing biogenicity. They showed that the ability to simultaneously map the distribution of organic elements [such as carbon (C), nitrogen (N), and sulfur (S)] and compare those element distributions with optically recognizable, cellularly preserved fossils could provide significant new insights into the origin of organic materials in ancient sediments. This chapter details a recent NanoSIMS study which was designed to acquire new data relevant to establishing critical biosignatures (Oehler et al., 2006a-c). In this study, NanoSIMS was used to characterize element distributions of spheroidal and filamentous microfossils and associated organic laminae in chert from the approx. 0.85 billion year old (Ga) Bitter Springs Formation of Australia. Previous work established preservation of a diverse microbiota in the Bitter Springs Formation (Schopf, 1968; Schopf and Blacic, 1971), and there is no dispute within the scientific community regarding the biogenicity of any of the Bitter Springs structures evaluated in this new study. Thus, the NanoSIMS results described below provide new insight into - and can be used as a guide for assessing - the origin of less well understood organic materials that may occur in early Archean samples and in meteorites or other extraterrestrial samples.

The urological complications of 320 consecutive renal transplants performed at our institution between October 17, 1985 and November 10, 1989 are reviewed. The Leadbetter-Politano technique of ureteroneocystostomy was used in the first 160 patients (group 1) and an anterior extravesical technique modified from the methods of Witzel, Sampson and Lich was performed in the second 160 patients (group 2). Urological complications occurred in 15 patients (9.4%) in group 1 and 6 (3.7%) in group 2 (p = 0.04). Ureterovesical junction obstruction occurred in 6 patients (3.7%) in group 1 and 1 (0.6%) in group 2 (p = 0.05). Complications of leakage, ureteral necrosis and ureteral stricture were comparable in the 2 groups. Therefore, we advocate the use of the anterior extravesical technique over Leadbetter-Politano ureteral reimplantation based on the lower incidence of urological complications and various technical advantages, including less operative time, avoidance of a separate cystotomy, less hematuria and ability to use short donor ureters.

Indigenous reduced carbon has been observed in the Martian meteorite Nakhla. For the first time we have analyzed the in situ carbon by a suite of micro-analytical techniques in order to identify and characterize the reduced carbonaceous matter. Optical analysis of the Nakhla petrographic thin-section revealed the existence of a dark brown/red vein-filling material appearing as a series of bifurcating intrusions into a fine (