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In situ Raman spectra of aqueous K2WO4-HCl, K2WO4-HCl-NaCl, and K2WO4-CO2-NaCl solutions were collected at elevated temperature (T, 100–400°C) and constant pressure (P) of 30 MPa. The stretching vibration band of the W=O bond (v1) was analyzed to reveal the species of tungsten (W) responsible for the hydrothermal transport of W during mineralization. Results showed that monomeric tungstates with v1(W=O) bands at ~930 and 950 cm-1 are the dominant W species in weakly alkaline (room temperature, pH=7.7) to near-neutral (room temperature, pH=7.2) solutions under the investigated T‐P conditions. Overall, the stability of polymeric tungstate species with v1(W=O) bands at ~965–995 cm-1 decreases with rising temperature and was not detected at ≥300°C in moderately acidic solution (room temperature, pH=4.9). However, increased fluid acidity and salinity obviously enlarged the temperature stability field of polymeric tungstate species. In highly acidic solution (room temperature, pH=1.4), polymeric tungstates are the only stable W species even at 400°C. In the presence of 1.9 mol/kg NaCl, polymeric tungstate(s) can persist to at least 350°C in moderately acidic solution. Considering that 300–350°C is the major W-mineralizing T range and W-mineralizing fluid is generally characterized by a moderately acidic nature, we propose that, in addition to monomeric tungstates, polymeric tungstates can also be important W species in some natural geological fluids that are responsible for the mineralization of W. Future studies of the W mineralization mechanism should take this issue into account.

The Guangshigou deposit is the largest pegmatite-type uranium deposit in the Shangdan domain of the North Qinling Orogenic Belt, which is characterized by the enrichment of uraninite hosted in biotite granitic pegmatites. At Guangshigou, uraninite commonly occurs as mineral inclusions in quartz, K-feldspar and biotite or in interstices of these rock-forming minerals with magmatic characteristics (e.g., U/Th &lt, 100, high ThO2, Y2O3 and REE2O3 contents and low concentrations of CaO, FeO and SiO2). It crystallized at 407.6 ± 2.9 Ma from fractionated calc-alkaline high-K pegmatitic melts under conditions of 470–700 °C and 2.4–3.4 kbar as deduced by the compositions of coexisting peritectic biotite. The primary uranium mineralization took place during the Late Caledonian post-collisional extension in the North Qinling Orogen. After this magmatic event, uraninite has experienced multiple episodes of fluid-assisted metasomatism, which generated an alteration halo of mineral assemblages. The alteration halo (or radiohalo) was the result of the combined effects of metamictization and metasomatism characterized by an assemblage of goethite, coffinite and an unidentified aluminosilicate (probably clay minerals) around altered uraninite. This fluid-assisted alteration was concomitant with the albitization of K-feldspar subsequently followed by the coffinitization of uraninite during the major period of 84.9–143.6 Ma, as determined by U-Th-Pb chemical ages. Further investigations revealed that the metasomatic overprinting on uraninite initially and preferentially took place along microcracks or cavities induced by metamictization and promoted their amorphization, followed by the release of U and Pb from structure and the incorporation of K, Ca and Si from the fluids, finally resulting in various degrees of uraninite coffinitization. The released U and Pb were transported by alkali-rich, relatively oxidizing fluids and then re-precipitated locally as coffinite and an amorphous U-Pb-rich silicate under low to moderate temperature conditions (85–174 °C). The compositional changes in primary uraninite, its structure amorphization together with the paragenetic sequence of secondary phases, therefore, corroborate a combined result of intense metamictization of uraninite and an influx of alkali–metasomatic fluids during the Late Mesozoic Yanshanian magmatic event in the region. Hence, the remobilization and circulation of uranium in the North Qinling Orogen was most likely driven by post-Caledonian magmatism and hydrothermal activities related to large-scale tectonic events. In this regards, Paleozoic pegmatite-type uranium mineralization may represent a significant uranium source for Mesozoic hydrothermal mineralization identified in the Qinling Orogenic Belt.

Pegmatite-type uranium mineralization occurs in the Shangdan domain of the North Qinling Orogenic Belt, representing a significant uraniferous province. The Guangshigou deposit is the largest U deposit of the district. Within the North Qinling area, a series of Caledonian granitic igneous rocks intruded the Proterozoic metamorphic rocks of the Qinling Group in two magmatic stages: (i) the Early Silurian Huichizi granite that was derived from a low degree of partial melting of thickened lower basaltic crust combined with mantle-derived materials following the subduction of the Shangdan Ocean, and (ii) the Late Silurian–Early Devonian Damaogou granite and associated pegmatites derived from the same source but emplaced in a late tectonic post-collisional extension environment. In the Guangshigou deposit, the U mineralization mainly occurs as uraninite disseminated in U-rich granitic biotite pegmatites, which formed by assimilation-fractional crystallization magmatic processes. Petrographic observations showed evidence for coeval crystallization of uraninite and other rock-forming minerals of the host pegmatite including quartz, feldspar, biotite, zircon, monazite, apatite, and xenotime. In addition, the low U/Th ratios (~19) and Th, REE, and Y enrichments characterized a magmatic origin for uraninite, which was likely derived from fractionated high-K calc-alkaline pegmatitic magma that experienced various degrees of crustal material contamination. In situ U-Pb isotopic dating performed by Secondary-Ion Mass Spectrometry (SIMS) on uraninite from the Guangshigou deposit yielded a crystallization age of 412 ± 3 Ma, which is concomitant (within errors) with the emplacement age of the host pegmatite (415 ± 2 Ma) and constrained the U ore genesis to the Early Devonian, which corresponds to the late Caledonian post-collisional extension in the North Qinling area. Uraninite then experienced various degrees of metamictization and/or post-Caledonian hydrothermal alteration characterized by an alteration rim associated with coffinite, chlorite and limonite. Finally, the characteristics of the pegmatite-related Guangshigou deposit exhibiting Th-rich uraninite which was the product of assimilation-fractional crystallization of pegmatitic magma defined a model significantly different than the one established for the world-class Rössing deposit characterized by Th-poor uraninite hosted in alaskite dykes formed by low degree of partial melting of U-rich metasediments.

The large low-grade Piaotang W–Sn deposit in the southern Jiangxi tungsten district of the eastern Nanling Range, South China, is related to a hidden granite pluton of Jurassic age. The magmatic-hydrothermal system displays a zonation from an inner greisen zone to quartz veins and to peripheral veinlets/stringers (Five-floor zonation model). Most mineralization is in quartz veins with wolframite > cassiterite. The hidden granite pluton in underground exposures comprises three intrusive units, i.e. biotite granite, two-mica granite and muscovite granite. The latter unit is spatially associated with the W–Sn deposit. Combined LA-MC-ICP-MS U–Pb dating of igneous zircon and LA-ICP-MS U–Pb dating of hydrothermal cassiterite are used to constrain the timing of granitic magmatism and hydrothermal mineralization. Zircon from the three granite units has a weighted average 206Pb/238U age of 159.8 ± 0.3 Ma (2 σ, MSWD = 0.3). The cathodoluminescence (CL) textures indicate that some of the cassiterite crystals from the wolframite-cassiterite quartz vein system have growth zonations, i.e. zone I in the core and zone II in the rim. Dating on cassiterite (zone II) yields a weighted average 206Pb/238U age of 159.5 ± 1.5 Ma (2 σ, MSWD = 0.4), i.e. the magmatic and hydrothermal systems are synchronous. This confirms the classical model of granite-related tin–tungsten mineralization, and is against the view of a broader time gap of >6 Myr between granite magmatism and W–Sn mineralization which has been previously proposed for the southern Jiangxi tungsten district. The elevated trace element concentrations of Zr, U, Nb, Ta, W and Ti suggest that cassiterite (zone II) formed in a high-temperature quartz vein system related to the Piaotang granite pluton.

Boron (B) is an important volatile component in many ore-forming fluids of hydrothermal deposits related to granites. The Maoping and Piaotang W-Sn deposits are typical magmatic-hydrothermal deposits located in South China. In this study, boron (i.e., H3BO3)-rich fluid inclusions are discovered in the above two deposits through in situ Raman spectrosocpic analyses. Based on careful experimental calibrations, we calculated the ratio of relative molar scattering factors between water and H3BO3 ( J H 2 O / J H 3 B O 3 ). In addition, the relationship between salinity and J H 2 O / J H 3 B O 3 was constructed. Then, Raman spectroscopic quantification of the NaCl-H3BO3-H2O solutions was proposed. Because corrections for the response function of the spectrometer and the influences of the wavenumber and temperature on the spectral intensity were applied, our Raman spectroscopic quantifications allow comparison across different laboratories. The salinity [mNaCl in m (mol/kg H2O)] and molality of B (mH3BO3) for topaz-hosted fluid inclusions at the Maoping W-Sn deposit were determined to be 0.29–1.48 m and 0.06–0.46 m, respectively. A large quartz crystal was collected from a wolframite-bearing quartz vein of the Piaotang W-Sn deposit. The H3BO3 concentration of fluid inclusions in this crystal was determined using Raman spectroscopy. From the core to the rim, mH3BO3 and mNaCl do not show monotonic changes; mH3BO3 fluctuates between 0.11 and 0.33 m, while mNaCl ranges from 0.11 to 1.41 m. Further thermodynamic calculations revealed moderately acidic ore-forming fluids with pH ranging from 4.9 to 5.1 at 23 °C. The fluctuation of mH3BO3 during the growth of a single quartz crystal indicates the episodic replenishment of magmatic-hydrothermal fluids. In addition, microthermometric measurement can result in non-negligible uncertainties in the fluid compostion determination for such complex NaCl-H2O-H3BO3-CO2-N2-CH4 fluid system. Alternatively, Raman spectroscopy can provide non-destructive and fast quantification of such fluid inclusions based on careful experimental calibrations.

The Volcanic-related Be-U-Mo Baiyanghe deposit is located in the Paleozoic Xuemisitan Volcanic Belt in West Junggar (NW China). It is the largest Be deposit in Asia which is dominantly hosted in late Devonian rhyolitic tuff and in the late Carboniferous Yangzhuang granite (313 ± 2 Ma) that were emplaced after the closure of the Junggar oceanic domain. The late Devonian rhyolitic tuff is a strongly fractionated peralkaline A1-type volcanic rock with a major magmatic enrichment in Nb, Y, Th, Be, Ta and U. Highly fractionated REE patterns and significant concentrations of Pb, Nb, Zr, Y, Th and Ta in the primary U mineralisation identified these tuffs as the dominant U and probably Be source for Be-U ore genesis in West Junggar. The primary high U concentrations (6.5 In the Baiyanghe deposit, structurally-controlled primary U mineralisation was temporally constrained by an in situ U-Pb isotopic minimum crystallisation age of 240 ± 7 Ma on pitchblende. This event represents the hydrothermal stage of U mineralisation that occurred during the early Permian–middle Triassic post-accretion event in West Junggar and paragenetically postdates the Be ore stage (ca. 303–265 Ma). The hydrothermal U mineralisation is mainly characterised by Pb-Nb-Ti-Zr-Mo-rich pitchblende veins associated with calcite and quartz, which crosscut Be-stage fluorite veins. During this episode of crustal extension, the Be-U-Mo ore therefore formed in a two-stage hydrothermal model within the same mineralising event: (i) oxidising meteoric and possibly basinal waters percolated downward into the basement through structures and mixed with CO2-bearing magmatic fluids derived from early generations of mafic dykes that intruded the host rocks in the Baiyanghe area. During the circulation of these thermal solutions along faults and fractured zones, Be was leached mainly from the Devonian rhyolitic tuff during hydrothermal alteration and dominantly transported as fluoride complexes in the fluids. These low-temperature (130–150 °C) ore solutions then reacted with Ca-rich minerals of the host rocks, which resulted in a pH increase that triggered fluorite precipitation in turn promoting Be deposition as bertrandite; and (ii) in a second stage, additional oxidising surface-derived fluids including meteoric waters and possibly basinal brines infiltrated the basement. U was also leached mainly from the late Devonian rhyolitic tuff and likely transported as chlorine and/or uranyl carbonate complexes in the fluids. U precipitated as pitchblende due to fO2 decrease when these low-temperature (120–125 °C) oxidising U-bearing solutions encountered favourable reducing environments mainly represented by dolerite and diabase dykes crosscutting the host rocks and/or carbonaceous shales at the contact with the Devonian rhyolitic tuff. Pitchblende then locally experienced dyke-emplacement related post-ore hydrothermal potassic alteration characterised by abundant illite crystallisation, significant Si gain and in situ relative enrichment of Nb, Ti, Th, and Ta due to strong U and Pb depletion. The primary U mineralisation was then largely oxidised into uranophane due to supergene alteration related to further meteoric water infiltration during late Mesozoic–Cenozoic crustal extension in West Junggar. The characteristics of the volcanic-related hydrothermal Be-U mineralisation in the Baiyanghe deposit show key similarities with Streltsovka (U-Mo-F) and Spor Mountain (Be-U) world-class districts, although Baiyanghe has much smaller resources than the ones in Streltsovka.

The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are growth factors. GLP-1 mimetics are on the market as treatments for type 2 diabetes. Both GLP-1 and GIP mimetics have shown neuroprotective properties in previous studies. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed to treat diabetes. Here, we report the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once daily (20 mg/kg intraperitoneally) for 7 days and the dual agonist was coinjected once daily (50 nmol/kg intraperitoneally). We found that the drug reduced most of the MPTP-induced motor impairments in the rotarod, open-field locomotion, and muscle strength test. The number of tyrosine hydroxylase-positive neurons in the substantia nigra and striatum was reduced by MPTP and increased by DA-JC1. Synapse numbers (synaptophysin expression) were reduced in the substantia nigra and the striatum by MPTP and DA-JC1 reversed this effect. The activation of a chronic inflammation response by MPTP was considerably reduced by the dual agonist (DA) (astroglia and microglia activation). Therefore, dual agonists show promise as a novel treatment of PD.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been shown to be neuroprotective in previous studies in animal models of Alzheimer's or Parkinson's disease. Recently, novel dual-GLP-1/GIP receptor agonists that activate both receptors (DA) were developed to treat diabetes. We tested the protective effects of a novel potent DA against middle cerebral artery occlusion injury in rats and compared it with a potent GLP-1 analog, Val(8)-GLP-1(glu-PAL). Animals were evaluated for neurologic deficit score, infarct volume, and immunohistochemical analyses of the brain at several time points after ischemia. The Val(8)-GLP-1(glu-PAL)-treated and DA-treated groups showed significantly reduced scores of neurological dysfunction, cerebral infarction size, and percentage of TUNEL-positive apoptotic neurons. Furthermore, the expression of the apoptosis marker Bax, the inflammation marker iNOS, and the survival marker Bcl-2 was significantly increased. The DA-treated group was better protected against neurodegeneration than the Val(8)-GLP-1(glu-PAL) group, and the scores of neurological dysfunction, cerebral infarction size, and expression of Bcl-2 were higher, whereas the percentage of TUNEL-positive neurons and the levels of Bax and iNOS were lower in the DA group. DA treatment reduced the infarct volume and improved the functional deficit. It also suppressed the inflammatory response and cell apoptosis after reperfusion. In conclusion, the novel GIP and GLP-1 dual-receptor agonist is more neuroprotective than a GLP-1 receptor agonist in key biomarkers of neuronal degeneration.

The growth factor glucagon-like peptide-1 (GLP-1) is neuroprotective in several animal models of neurodegeneration. Here, we analyzed the neuroprotective effects of a novel protease-resistant GLP-1 analogue, (Val 8 )GLP-1-Glu-PAL, which has advantages over older analogues, such as improvement of hippocampal neurogenesis, glucose homeostasis, and insulin secretion. We established an in vitro model of Parkinson's disease using the mitochondrial stressor rotenone in primary cultured mouse neurons pretreated with (Val 8 )GLP-1-Glu-PAL. (Val 8 )GLP-1-Glu-PAL alone did not affect neuronal viability, but prevented the rotenone-induced reduction in cell viability in a dose-dependent manner. In addition, (Val 8 )GLP-1-Glu-PAL pretreatment prevented rotenone-induced proapoptotic changes manifesting as downregulation of procaspase-3 and Bcl-2 and upregulation of cleaved caspase-3. These results demonstrate that the novel agent (Val 8 )GLP-1-Glu-PAL shows promise as a drug treatment for Parkinson's disease.

Knowledge on hydrothermal tungsten (W) species is vital towards a better understanding of tungsten transport and mineralization mechanisms. In this study, in situ Raman spectra of a 0.005 – 0.1 mol/kg (m) K2WO4 solution containing CO2, HCl, and NaHCO3 were collected at 50–400 °C and 20–60 MPa. The spectra for the symmetric stretching vibration mode of the W O bond, v1(W O), were analyzed to investigate the hydrothermal tungstate species. Results showed that carbonate/bicarbonate do not associate with tungstate to form carbonic tungstate species. Nevertheless, the presence of CO2 can increase the fluid acidity, which favors the formation of polymeric tungstate species at O) modes of these species are centered at ∼930 cm-1 and 950 cm-1. Based on the above observations, we simulated the mineralization process in the context of fluid-rock interactions using tungstate and alkali tungstate ion pairs as the only aqueous W species. The thermodynamic simulations showed that (a) the timing of mineralization mainly depends on the W concentration in the initial mineralizing fluid and the availability of Ca2+, Fe2+ and Mn2+, with higher W concentrations generally favoring higher temperature mineralization; (b) highly W-enriched fluid is not essential for W mineralization, while extremely low contents of Fe, Mn and Ca in the magma are useful to maintain the mobility of aqueous W until favorable host rocks are encountered; and (c) a “hydrogen reservoir” effect was identified for dissolved CO2. The presence of CO2 can promote the extraction of Fe(II) from the pelitic host rocks, thereby facilitating a high-grade vein-type W mineralization. At O) modes are centered at ∼965 – 995 cm-1, are important hydrothermal W species along with monomeric tungstates. Therefore, polymeric tungstate species should be considered in future thermodynamic modeling of W transport and mineralization at

Development of nuclear energy needs the support of considerable uranium reserves. Danfeng uranium ore-fields was the unique pegmatite-type uranium deposits been found in China. Characteristic, mineral paragenesis, alteration and secondary-mineral-assemble of uraninite in this area been studied by Microscope, SEM and EPMA. The results revealed: 1) Uraninite was the only primary uranium mineral, displayed in automorphic-hypautomorpuic granular texture, disseminated embedded within gangue minerals or among their grains. 2) U, Th and Pb were the major elements,Y, Ca, Si, Na, Hf, Fe, Zr, Mg, P, Mn were the minor elements in uraninite. 3) Uraninite subjected to hydrothermal alteration and some of it were surrounded by secondary minerals included secondary uranium minerals, sulfide, oxides and other silicate minerals. 4) Mineralization of uranium was mainly controlled by crystallization differentiation of primary pegmatitic magma, later hydrothermal alteration and/or supergenetic oxidation had influence on it.

Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sought to identify an anti-apoptotic mechanism for the treatment of neurodegenerative diseases. Primary cultured neurons were treated with different concentrations of rotenone for 48 hours. Morphological observation, cell counting kit-8 assay, lactate dehydrogenase detection and western blot assay demonstrated that 0.5 nM rotenone increased lactate dehydrogenase release, decreased the expression of procaspase-3 and Bcl-2, and increased cleaved caspase-3 expression in normal neurons. All these effects were prevented by geniposide. Our results indicate that geniposide diminished rotenone-induced injury in primary neurons by suppressing apoptosis. This may be one of the molecular mechanisms underlying the efficacy of geniposide in the treatment of neurodegenerative diseases.

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Background We aimed to determine the risk conferred by metabolic syndrome ( METS ) and diabetes mellitus ( DM ) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High‐risk patients with Acute Non‐disabling Cerebrovascular Events) trial. Methods and Results In total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society ( CDS ) and International Diabetes Foundation ( IDF ) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS , 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow‐up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89–3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98–3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke ( P =0.82 for interaction in the fully adjusted model of CDS ) was observed. Using the METS ( IDF ) criteria demonstrated similar results. Conclusions Concurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack.

Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD. Recently, dual GLP-1/GIP receptor agonists have been developed. We therefore tested the novel dual agonist DA3-CH in comparison with the best GLP-1 analogue currently on the market, liraglutide (both drugs 25nmol/kg ip once-daily for 7 days) in the MPTP mouse model of PD (25 mg/kg ip once-daily for 7 days). In the Rotarod and grip strength assessment, DA3-CH was superior to liraglutide in reversing the MPTP–induced motor impairment. Dopamine synthesis as indicated by levels of tyrosine hydroxylase was much reduced by MPTP in the substantia nigra and striatum, and DA3-CH reversed this while liragutide only partially reversed this. The chronic inflammation response as shown in increased levels of activated microglia and astrocytes was reduced by both drugs. Importantly, expression levels of the neuroprotective growth factor Glial Derived Neurotrophic Factor (GDNF) was much enhanced by both DA3-CH and liragutide. The results demonstrate that the combination of GLP-1 and GIP receptor activation is superior to single GLP-1 receptor activation alone. Therefore, new dual agonists may be a promising treatment for PD. The GLP-1 receptor agonist exendin-4 has already shown disease modifying effects in clinical trials in PD patients.

Stroke is a condition with few medical treatments available. Semaglutide, a novel Glucagon-like peptide-1 (GLP-1) analogue, has been brought to the market as a treatment for diabetes. We tested the protective effects of semaglutide against middle cerebral artery occlusion injury in rats. Animals were treated with 10 nmol/kg bw ip. starting 2 h after surgery and every second day for either 1, 7, 14 or 21 days. Semaglutide-treated animals showed significantly reduced scores of neurological impairments in several motor and grip strength tasks. The cerebral infarction size was also reduced, and the loss of neurons in the hippocampal areas CA1, CA3 and the dentate gyrus was much reduced. Chronic inflammation as seen in levels of activated microglia and in the activity of the p38 MAPK – MKK – c-Jun- NF-κB p65 inflammation signaling pathway was reduced. In addition, improved growth factor signaling as shown in levels of activated ERK1 and IRS-1, and a reduction in the apoptosis signaling pathway C-raf, ERK2, Bcl-2/BAX and Caspase-3 was observed. Neurogenesis had also been normalized by the drug treatment as seen in increased neurogenesis (DCX-positive cells) in the dentate gyrus and a normalization of biomarkers for neurogenesis. In conclusion, semaglutide is a promising candidate for re-purposing as a stroke treatment.

Microbes inhabiting Earth have adapted to diverse environments of water, air, soil, and often at the interfaces of multiple media. In this study, we focus on the behavior of Caulobacter crescentus, a singly flagellated bacterium, at the air/water interface. Forward swimming C. crescentus swarmer cells tend to get physically trapped at the surface when swimming in nutrient-rich growth medium but not in minimal salt motility medium. Trapped cells move in tight, clockwise circles when viewed from the air with slightly reduced speed. Trace amounts of Triton X100, a nonionic surfactant, release the trapped cells from these circular trajectories. We show, by tracing the motion of positively charged colloidal beads near the interface that organic molecules in the growth medium adsorb at the interface, creating a high viscosity film. Consequently, the air/water interface no longer acts as a free surface and forward swimming cells become hydrodynamically trapped. Added surfactants efficiently partition to the surface, replacing the viscous layer of molecules and reestablishing free surface behavior. These findings help explain recent similar studies on Escherichia coli, showing trajectories of variable handedness depending on media chemistry. The consistent behavior of these two distinct microbial species provides insights on how microbes have evolved to cope with challenging interfacial environments.

The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors with neuroprotective properties. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. Both GLP-1 and GIP mimetics have shown neuroprotective properties in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed and are tested in diabetic patients. Here we demonstrate the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20 mg/kg i.p.) for 7 days, and the dual agonist was injected 30 min later i.p. (50 nmol/kg bw). The PI3k inhibitor LY294002 (0.6 mg/kg i.v.) was co-injected in one group. DA-JC1 reduced or reversed most of the MPTP induced motor impairments in the rotarod and in a muscle strength test. The number of tyrosine hydroxylase (TH) positive neurons in the substantia nigra (SN) was reduced by MPTP and increased by DA-JC1. The ratio of anti-inflammatory Bcl-2 to pro-inflammatory BAX as well as the activation of the growth factor kinase Akt was reduced by MPTP and reversed by DA-JC1. The PI3k inhibitor had only limited effect on the DA-JC1 drug effect. Importantly, levels of the neuroprotective brain derived neurotropic factor (BDNF) were reduced by MPTP and enhanced by DA-JC1. The results demonstrate that DA-JC1 shows promise as a novel treatment for PD.

Glucose-dependent insulinotropic polypeptide (GIP) is a member of the incretin hormones and growth factors. Neurons express the GIP receptor, and GIP and its agonists can pass through the blood brain barrier and show remarkable neuroprotective effects by protecting synapse function and numbers, promoting neuronal proliferation, reducing amyloid plaques in the cortex and reducing the chronic inflammation response of the nervous system. Long-acting analogues of GIP that are protease resistant had been developed as a treatment for type 2 diabetes. It has been found that such GIP analogues show good protective effects in animal models of Alzheimer’s disease. Novel dual agonist peptides that activate the GIP receptor and another incretin receptor, glucagon-like peptide -1 (GLP-1), are under development that show superior effects in diabetic patients compared to single GLP-1 agonists. The dual agonists also show great promise in treating neurodegenerative disorders, and there are currently several clinical trials ongoing, testing GLP-1 mimetics in people with Alzheimer’s or Parkinson’s disease.

Most nanomaterials enter the natural environment as nanoenabled products, which are typically composites with primary nanoparticles bound on substrates or embedded in liquid or solid matrices. The environmental risks associated with these products are expected to differ from those associated with the as-produced particles. This article presents a case study on the end-of-life emission of a commercial prototype polymer/quantum-dot (QD) composite used in solid-state lighting for homes. We report the extent of cadmium release upon exposure to a series of environmental and biological simulant fluids, and track the loss of QD-characteristic fluorescence as a marker for chemical damage to the CdSe/ZnS nanoparticles. Measured cadmium releases after 30-day exposure range from 0.007 to 1.2 mg/g of polymer, and the higher values arise for low-pH simulants containing nitric or gastric acid. Centrifugal ultrafiltration and ICP was used to distinguish soluble cadmium from particulate forms. The leachate is found to contain soluble metals with no evidence of free QDs or QD-containing polymeric debris. The absence of free nanoparticles suggests that this product does not raise nanotechnology-specific environmental issues associated with degradation and leaching, but is more usefully regarded as a conventional chemical product that is a potential source of small amounts of soluble cadmium.

The attachment of bacteria to surfaces provides advantages such as increasing nutrient access and resistance to environmental stress. Attachment begins with a reversible phase, often mediated by surface structures such as flagella and pili, followed by a transition to irreversible attachment, typically mediated by polysaccharides. Here we show that the interplay between pili and flagellum rotation stimulates the rapid transition between reversible and polysaccharide-mediated irreversible attachment. We found that reversible attachment of Caulobacter crescentus cells is mediated by motile cells bearing pili and that their contact with a surface results in the rapid pili-dependent arrest of flagellum rotation and concurrent stimulation of polar holdfast adhesive polysaccharide. Similar stimulation of polar adhesin production by surface contact occurs in Asticcacaulis biprosthecum and Agrobacterium tumefaciens. Therefore, single bacterial cells respond to their initial contact with surfaces by triggering just-in-time adhesin production. This mechanism restricts stable attachment to intimate surface interactions, thereby maximizing surface attachment, discouraging non-productive self-adherence, and preventing curing of the adhesive.

The Tieshanlong tungsten-polymetallic deposit is a large wolframite deposit of quartz vein type located in southern Jiangxi, South China. It is genetically related to a high-K S-type granite. Seven pyrite and two wolframite samples, selected for He and Ar isotope analyses, yielded 3He/4He values of 0.04–0.98 Ra, 40Ar/36Ar ratios of 293.5–368.0, and 38Ar/36Ar ratios of 0.176–0.193. These data indicate that the ore-forming fluids associated with the deposit did not result from a simple mixing of the crustal- and mantle-derived end-member fluids, but that primeval meteoric fluids were also involved in the generation of the associated granitic magma by partial melting of crustal metasedimentary rocks. Further investigations show that only minimal He from the mantle was added during generation of the associated granitic magma. It is postulated that boiling and second mixing with “new” meteoric fluids took place during migration of magmatic-hydrothermal fluids into wall-rock fractures, resulting in a drastic decrease of their metal transport capacity, which triggered the tungsten-polymetallic mineralization.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme for heme catabolism and iron production, its role in intracerebral hemorrhage (ICH) is controversial. The study was to investigate correlations between brain oxidative injury and HO-1 after experimental ICH.Sprague-Dawley rats received intra-striatal infusions of 100 μl autologous whole blood as ICH models. HO-1 were examined by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) analysis. Brain oxidative stress was quantitated by malondialdehyde (MDA); antioxidation were measured by copper-zinc superoxide dismutase (Cu/Zn-SOD) activity using RT-PCR assay.The expression of the HO-1 upregulated and reached its peak at days 3 and 7 after ICH (P 0.01). There was a significant increase of MDA and a top at 3-day post-ICH (P 0.01); Cu/Zn-SOD was upregulated post-ICH and reached the top at day 7 (P 0.001); HO-1 was correlated significantly with brain MDA content at days 7 and 14 following ICH (r = 0.435-0.501, P 0.001) but there is no definite correlation between them on 1 to 3 days (P 0.05); conversely, HO-1 was correlated significantly with Cu/Zn-SOD on 1 to 3 days after ICH (r = 0.433-0.621, P 0.001) but there is no definite correlation between them at days 7 and 14 (P 0.05).HO-1 has both antioxidant and prooxidant properties in ICH. The early upregulation of HO-1 possibly fit with the events and be protective against oxidative stress, whereas its overexpression in the late stages may result in its dysfunction and be toxic. So it should be prudent to intervene ICH with the inhibitor/activator of HO-1.

Brownian motion influences bacterial swimming by randomizing displacement and direction. Here, we report that the influence of Brownian motion is amplified when it is coupled to hydrodynamic interaction. We examine swimming trajectories of the singly flagellated bacterium Caulobacter crescentus near a glass surface with total internal reflection fluorescence microscopy and observe large fluctuations over time in the distance of the cell from the solid surface caused by Brownian motion. The observation is compared with computer simulation based on analysis of relevant physical factors, including electrostatics, van der Waals force, hydrodynamics, and Brownian motion. The simulation reproduces the experimental findings and reveals contribution from fluctuations of the cell orientation beyond the resolution of present observation. Coupled with hydrodynamic interaction between the bacterium and the boundary surface, the fluctuations in distance and orientation subsequently lead to variation of the swimming speed and local radius of curvature of swimming trajectory. These results shed light on the fundamental roles of Brownian motion in microbial motility, nutrient uptake, and adhesion.

Bacterial chemotaxis relies on the clockwise-to-counterclockwise switching (and the reverse CCW-to-CW switching) of the flagellar motor’s rotational direction. Yet, despite its central role, the switch mechanism remains poorly understood. Here we study the switch statistics of the flagellar motor using computer simulations that combine first-passage time ideas and the property of dynamic binding of CheY-P to FliM. The simulated clockwise bias and switching frequency as a function of CheY-P concentration agree with the experimental results for E. coli. Moreover, the simulation results show a robust peak, which is present in some experimental reports, in the distribution of the time intervals of both clockwise and counterclockwise rotation.

A Caulobacter crescentus swarmer cell is propelled by a helical flagellum, which is rotated by a motor at its base. The motor alternates between rotating in clockwise and counterclockwise directions and spends variable intervals of time in each state. We measure the distributions of these intervals for cells either free swimming or tethered to a glass slide. A peak time of around one second is observed in the distributions for both motor directions with counterclockwise intervals more sharply peaked and clockwise intervals displaying a larger tail at long times. We show that distributions of rotation intervals fit first passage time statistics for a biased random walker and the dynamic binding of CheY-P to FliM motor subunits accounts for this behavior. Our results also suggest that the presence of multiple CheY proteins in C. crescentus may be responsible for differences between its switching behavior and that of the extensively studied E. coli.

Glucagon-like peptide 1 (GLP-1) is a growth factor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a clinical trial in PD patients showed promising first results. Liraglutide and lixisenatide are two newer GLP-1 mimetics which have a longer biological half-life than exendin-4. We previously showed that these drugs have neuroprotective properties in an animal model of Alzheimer's disease. Here we demonstrate the neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20mg/kg i.p.) for 7 days, and drugs were injected once-daily for 14 days i.p. When comparing exendin-4 (10 nmol/kg), liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen. Both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro-apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The results demonstrate that in this study, both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of PD.

A growing body of evidence has linked two of the most common aged-related diseases: type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). It has led to the notion that drugs developed for the treatment of T2DM may be beneficial in modifying the pathophysiology of AD. As a receptor agonist of glucagon-like peptide-1 (GLP-1R), which is a newer drug class to treat T2DM, geniposide shows clear effects in inhibiting pathological processes underlying AD, such as promoting neurite outgrowth. In the present article, we review the possible molecular mechanisms of geniposide to protect the brain from pathologic damages underlying AD: reducing amyloid plaques, inhibiting τ phosphorylation, preventing memory impairment and loss of synapses, reducing oxidative stress and the chronic inflammatory response, and promoting neurite outgrowth via the GLP-1R signaling pathway. In summary, the Chinese herb geniposide shows great promise as a novel treatment for AD.

The adhesion of bacteria to surfaces plays critical roles in the environment, disease, and industry. In aquatic environments, Caulobacter crescentus is one of the first colonizers of submerged surfaces. Using a micromanipulation technique, we measured the adhesion force of single C. crescentus cells attached to borosilicate substrates through their adhesive holdfast. The detachment forces measured for 14 cells ranged over 0.11 to 2.26 μN, averaging 0.59 ± 0.62 μN. Based on the calculation of stress distribution with the finite element analysis method (dividing an object into small grids and calculating relevant parameters for all of the elements), the adhesion strength between the holdfast and the substrate is >68 N/mm 2 in the central region of contact. To our knowledge, this strength of adhesion is the strongest ever measured for biological adhesives.

The aquatic bacterium Caulobacter crescentus attaches to solid surfaces through an adhesive holdfast located at the tip of its polar stalk, a thin cylindrical extension of the cell membrane. In this paper, the elastic properties of the C. crescentus stalk and holdfast assembly were studied by using video light microscopy. In particular, the contribution of oligomers of N -acetylglucosamine (GlcNAc) to the elasticity of holdfast was examined by lysozyme digestion. C. crescentus cells attached to a surface undergo Brownian motion while confined effectively in a harmonic potential. Mathematical analysis of such motion enabled us to determine the force constant of the stalk-holdfast assembly, which quantifies its elastic properties. The measured force constant exhibits no dependence on stalk length, consistent with the theoretical estimate showing that the stalk can be treated as a rigid rod with respect to fluctuations of the attached cells. Therefore, the force constant of the stalk-holdfast assembly can be attributed to the elasticity of the holdfast. Motions of cells in a rosette were found to be correlated, consistent with the elastic characteristics of the holdfast. Atomic force microscopy analysis indicates that the height of a dried (in air) holdfast is approximately one-third of that of a wet (in water) holdfast, consistent with the gel-like nature of the holdfast. Lysozyme, which cleaves oligomers of GlcNAc, reduced the force constant to less than 10% of its original value, consistent with the polysaccharide gel-like nature of the holdfast. These results also indicate that GlcNAc polymers play an important role in the strength of the holdfast.

Nanometer-scale bubbles (nanobubbles) have been produced by a special method on solid surfaces. The atomic force microscope used to detect these nanobubbles showed that they can be seen on liquid/graphite and liquid/mica interfaces. The conformation of the bubbles was influenced by the atomic steps of the graphite substrate. In addition, shadows found around the bubbles were attributed to the interactions between a bubble adhered to the tip and the bubbles on the surface.

This study aimed to determine the effects of different concentrations of soluble beta-amyloid 25-35 (Aβ25-35) on cell viability, calcium overload, and PI3K-p85 expression in cultured cortical rat neurons. Primary cultured cerebral cortical neurons of newborn rats were divided randomly into six groups. Five groups were treated with soluble Aβ25-35 at concentrations of 10nmol/L, 100nmol/L, 1μmol/L, 10μmol/L, or 30μmol/L. Cell Counting Kit-8 staining was used to measure cell viability, laser-scanning confocal imaging was used to detect changes in intracellular free calcium concentration, and western blot assay was used to measure neuronal PI3K-p85 expression. Soluble Aβ25-35 was found to reduce cell viability and induce calcium overload in primary cultured rat cerebral cortical neurons, in a concentration-dependent manner. At certain concentrations, soluble Aβ25-35 also increased neuronal PI3K-p85 expression. These findings reveal that soluble Aβ25-35 reduces the viability of cultured cerebral cortical rat neurons. The neurotoxicity mechanism may involve calcium overload and disruption of insulin signal transduction pathways.

Microstructures of potassium hexatitanate (K2Ti6O13) whiskers prepared by calcination of KF and TiO2 mixture were studied through high-resolution electron microscopy. The rod axis of a K2Ti6O13 whisker is along the [010] direction. These whiskers normally have a lamellar structure in their longitudinal direction, and adjacent lamellae usually have the same crystallographic orientation. Each lamella might be further divided into several fine layers with a width on the nanometer scale in the same crystallographic orientation. The whisker can be split in the longitudinal direction along either the boundary between two lamellae or the weak binding crystal plane, such as (100) and (201) planes. The mechanisms for the formation of lamella and layer structures and for the splitting of whiskers are discussed.

Potassium hexatitanate (K2Ti6O13) whiskers with an average thickness of less than 100 nm were synthesized by calcinating KF and TiO2 mixtures and subsequent boiling water treatment and reheating. The influences of heating temperature and weight ratio of KF to TiO2 in the mixture on the formation of K2Ti6O13 whiskers were investigated. The suitable experiment condition for whisker formation is a weight ratio of KF to TiO2 of about 2:1 and a heating temperature of about 720 degrees C. The resultants of reactions between KF and TiO2 at 720 degrees C were investigated by selected area diffraction (SAD) technique. Some new structures having a monoclinic structure with b = 0.38 nm were found. All these compounds transformed into K2Ti6O13 after boiling water treatment and reheating, (C) 2000 Elsevier Science Ltd.

Rutile TiO2 nanowhiskers have been synthesized by annealing a precursor powder in which NaCl and Ti(OH)4 particles were homogeneously mixed. The precursor powder was prepared by mixing three kinds of inverse microemulsions (μE) containing TiCl4 aqueous solution, ammonia, and NaCl aqueous solution, respectively, followed by washing with acetone. Annealing temperature and packing density of Ti(OH)4 in the precursor powder influenced the formation of rutile nanowhiskers. The optimum temperature was 750 °C. TiO2 nanowhiskers obtained by annealing a precursor powder in which the molar ratio of sodium to titanium was 400 at 750 °C for 2 h had diameters of 10–50 nm and lengths of several micrometers. They were straight rods with square cross sections, and the side surfaces were composed of four equivalent {110} planes.

Background Adhesion to surfaces facilitates many crucial functions of microbes in their natural habitats. Thus understanding the mechanism of microbial adhesion is of broad interest to the microbiology research community. Results We report a study by fluorescence imaging and atomic force microscopy on the growth in size and thickness of the holdfast of synchronized Caulobacter crescentus cells as they attach to a glass surface. We found that the holdfast undergoes a two-stage process of spreading and thickening during its morphogenesis. The holdfast first forms a thin plate on the surface. The diameter of the holdfast plate reaches its final average value of 360 nm by the cell age of ~ 30 min, while its thickness further increases until the age of ~ 60 min. Our AFM analysis indicates that the holdfast is typically thicker in the middle, with gradual falloff in thickness towards the outer edge. Conclusions We propose that the newly secreted holdfast substance is fluid-like. It has strong affinity to the surface and cures to form a plate-like holdfast capable of supporting strong and permanent adhesion.

Monodisperse 11 nm indium tin oxide (ITO) nanocrystals (NCs) were synthesized by thermal decomposition of indium acetylacetonate, In(acac)(3), and tin bis(acetylacetonate)dichloride, Sn(acac)(2)Cl(2), at 270 °C in 1-octadecene with oleylamine and oleic acid as surfactants. Dispersed in hexane, these ITO NCs were spin-cast on centimeter-wide glass substrates, forming uniform ITO NC assemblies with root-mean-square roughness of 2.9 nm. The assembly thickness was controlled by ITO NC concentrations in hexane and rotation speeds of the spin coater. Via controlled thermal annealing at 300 °C for 6 h under Ar and 5% H(2), the ITO NC assemblies became conductive and transparent with the 146 nm-thick assembly showing 5.2 × 10(-3) Ω·cm (R(s) = 356 Ω/sq) resistivity and 93% transparency in the visible spectral range--the best values ever reported for ITO NC assemblies prepared from solution phase processes. The stable hexane dispersion of ITO NCs was also readily spin-cast on polyimide (T(g) ~360 °C), and the resultant ITO assembly exhibited a comparable conductivity and transparency to the assembly on a glass substrate. The reported synthesis and assembly provide a promising solution to the fabrication of transparent and conducting ITO NCs on flexible substrates for optoelectronic applications.

The attachment of bacteria to surfaces provides advantages such as increasing nutrient access and resistance to environmental stress. Attachment begins with a reversible phase, often mediated by surface structures such as flagella and pili, followed by a transition to irreversible attachment, typically mediated by polysaccharides. Here we show that the interplay between pili and flagellum rotation stimulates the rapid transition between reversible and polysaccharide-mediated irreversible attachment. We found that reversible attachment of Caulobacter crescentus cells is mediated by motile cells bearing pili and that their contact with a surface results in the rapid pili-dependent arrest of flagellum rotation and concurrent stimulation of polar holdfast adhesive polysaccharide. Similar stimulation of polar adhesin production by surface contact occurs in Asticcacaulis biprosthecum and Agrobacterium tumefaciens. Therefore, single bacterial cells respond to their initial contact with surfaces by triggering just-in-time adhesin production. This mechanism restricts stable attachment to intimate surface interactions, thereby maximizing surface attachment, discouraging non-productive self-adherence, and preventing curing of the adhesive.

We measured the distribution of a forward swimming strain of Caulobacter crescentus near a surface using a three-dimensional tracking technique based on dark field microscopy and found that the swimming bacteria accumulate heavily within a micrometer from the surface. We attribute this accumulation to frequent collisions of the swimming cells with the surface, causing them to align parallel to the surface as they continually move forward. The extent of accumulation at the steady state is accounted for by balancing alignment caused by these collisions with the rotational Brownian motion of the micrometer-sized bacteria. We performed a simulation based on this model, which reproduced the measured results. Additional simulations demonstrate the dependence of accumulation on swimming speed and cell size, showing that longer and faster cells accumulate more near a surface than shorter and slower ones do.

Bacterial flagella play key roles in surface attachment and host-bacterial interactions as well as driving motility. Here, we have investigated the ability of Caulobacter crescentus to assemble its flagellar filament from six flagellins: FljJ, FljK, FljL, FljM, FljN, and FljO. Flagellin gene deletion combinations exhibited a range of phenotypes from no motility or impaired motility to full motility. Characterization of the mutant collection showed the following: (i) that there is no strict requirement for any one of the six flagellins to assemble a filament; (ii) that there is a correlation between slower swimming speeds and shorter filament lengths in Δ fljK Δ fljM mutants; (iii) that the flagellins FljM to FljO are less stable than FljJ to FljL; and (iv) that the flagellins FljK, FljL, FljM, FljN, and FljO alone are able to assemble a filament.

In this letter we propose a kinematic model to explain how collisions with a surface and rotational Brownian motion give rise to accumulation of micro-swimmers near a surface. In this model, an elongated microswimmer invariably travels parallel to the surface after hitting it from an oblique angle. It then swims away from the surface, facilitated by rotational Brownian motion. Simulations based on this model reproduce the density distributions measured for the small bacteria E. coli and Caulobacter crescentus, as well as for the much larger bull spermatozoa swimming between two walls.

nanjing univ, natl lab solid state microstruct, nanjing 210093, peoples r china. acad sinica, inst met res, atom imaging solids lab, shenyang 110015, peoples r china. nanjing univ, modern anal ctr, nanjing 210093, peoples r china.;li, gl (reprint author), nanjing univ, natl lab solid state microstruct, nanjing 210093, peoples r china

We determined the torque of the flagellar motor of Caulobacter crescentus for different motor rotation rates by measuring the rotation rate and swimming speed of the cell body and found it to be remarkably different from that of other bacteria, such as Escherichia coli and Vibrio alginolyticus. The average stall torque of the Caulobacter flagellar motor was approximately 350 pN nm, much smaller than the values of the other bacteria measured. Furthermore, the torque of the motor remained constant in the range of rotation rates up to those of freely swimming cells. In contrast, the torque of a freely swimming cell for V. alginolyticus is typically approximately 20% of the stall torque. We derive from these results that the C. crescentus swarmer cells swim more efficiently than both E. coli and V. alginolyticus. Our findings suggest that C. crescentus is optimally adapted to low nutrient aquatic environments.