RasGAP Shields Akt from Deactivating Phosphatases in Fibroblast Growth Factor Signaling but Loses This Ability Once Cleaved by Caspase-3.

Fibroblast growth factor receptors (FGFRs) are involved in proliferative and differentiation physiological responses. Deregulation of FGFR-mediated signaling involving the Ras/PI3K/Akt and the Ras/Raf/ERK MAPK pathways is causally involved in the development of several cancers. The caspase-3/p120 RasGAP module is a stress sensor switch. Under mild stress conditions, RasGAP is cleaved by caspase-3 at position 455. The resulting N-terminal fragment, called fragment N, stimulates anti-death signaling. When caspase-3 activity further increases, fragment N is cleaved at position 157. This generates a fragment, called N2, that no longer protects cells. Here, we investigated in Xenopus oocytes the impact of RasGAP and its fragments on FGF1-mediated signaling during G2/M cell cycle transition. RasGAP used its N-terminal Src homology 2 domain to bind FGFR once stimulated by FGF1, and this was necessary for the recruitment of Akt to the FGFR complex. Fragment N, which did not associate with the FGFR complex, favored FGF1-induced ERK stimulation, leading to accelerated G2/M transition. In contrast, fragment N2 bound the FGFR, and this inhibited mTORC2-dependent Akt Ser-473 phosphorylation and ERK2 phosphorylation but not phosphorylation of Akt on Thr-308. This also blocked cell cycle progression. Inhibition of Akt Ser-473 phosphorylation and entry into G2/M was relieved by PHLPP phosphatase inhibition. Hence, full-length RasGAP favors Akt activity by shielding it from deactivating phosphatases. This shielding was abrogated by fragment N2. These results highlight the role played by RasGAP in FGFR signaling and how graded stress intensities, by generating different RasGAP fragments, can positively or negatively impact this signaling

Fluctuations in Ammonia Oxidizing Communities Across Agricultural Soils are Driven by Soil Structure and pH

The milieu in soil in which microorganisms dwell is never constant. Conditions such as temperature, water availability, pH and nutrients frequently change, impacting the overall functioning of the soil system. To understand the effects of such factors on soil functioning, proxies (indicators) of soil function are needed that, in a sensitive manner, reveal normal amplitude of variation. Thus, the so-called normal operating range (NOR) of soil can be defined. In this study we determined different components of nitrification by analyzing, in eight agricultural soils, how the community structures and sizes of ammonia oxidizing bacteria and archaea (AOB and AOA, respectively), and their activity, fluctuate over spatial and temporal scales. The results indicated that soil pH and soil type are the main factors that influence the size and structure of the AOA and AOB, as well as their function. The nitrification rates varied between 0.11 ± 0.03 μgN h−1 gdw−1 and 1.68 ± 0.11 μgN h−1 gdw−1, being higher in soils with higher clay content (1.09 ± 0.12 μgN h−1 gdw−1) and lower in soils with lower clay percentages (0.27 ± 0.04 μgN h−1 gdw−1). Nitrifying activity was driven by soil pH, mostly related to its effect on AOA but not on AOB abundance. Regarding the influence of soil parameters, clay content was the main soil factor shaping the structure of both the AOA and AOB communities. Overall, the potential nitrifying activities were higher and more variable over time in the clayey than in the sandy soils. Whereas the structure of AOB fluctuated more (62.7 ± 2.10%) the structure of AOA communities showed lower amplitude of variation (53.65 ± 3.37%). Similar trends were observed for the sizes of these communities. The present work represents a first step toward defining a NOR for soil nitrification. The sensitivity of the process and organisms to impacts from the milieu support their use as proxies in the NOR of agricultural soils. Moreover, the clear effect of soil texture established here suggests that the NOR should be defined in a soil type-specific manner

KP line solitons and Tamari lattices

The KP-II equation possesses a class of line soliton solutions which can be qualitatively described via a tropical approximation as a chain of rooted binary trees, except at "critical" events where a transition to a different rooted binary tree takes place. We prove that these correspond to maximal chains in Tamari lattices (which are poset structures on associahedra). We further derive results that allow to compute details of the evolution, including the critical events. Moreover, we present some insights into the structure of the more general line soliton solutions. All this yields a characterization of possible evolutions of line soliton patterns on a shallow fluid surface (provided that the KP-II approximation applies).Comment: 49 pages, 36 figures, second version: section 4 expande

AS-771-13 Resolution on Proposal for the Establishment of the Kenneth N. Edwards Western Coatings Technology Center

That The Academic Senate endorses the proposal for the Kenneth N. Edwards Western Coatings Technology Center

Genomic Characterization of the Guillain-Barre Syndrome-Associated Campylobacter jejuni ICDCCJ07001 Isolate

Campylobacter jejuni ICDCCJ07001 (HS:41, ST2993) was isolated from a Guillain-Barré syndrome (GBS) patient during a 36-case GBS outbreak triggered by C. jejuni infections in north China in 2007. Sequence analysis revealed that the ICDCCJ07001 genome consisted of 1,664,840 base pairs (bp) and one tetracycline resistance plasmid of 44,084 bp. The GC content was 59.29% and 1,579 and 37 CDSs were identified on the chromosome and plasmid, respectively. The ICDCCJ07001 genome was compared to C. jejuni subsp. jejuni strains 81-176, 81116, NCTC11168, RM1221 and C. jejuni subsp. doylei 269.97. The length and organization of ICDCCJ07001 was similar to that of NCTC11168, 81-176 and 81-116 except that CMLP1 had a reverse orientation in strain ICDCCJ07001. Comparative genomic analyses were also carried out between GBS-associated C. jejuni strains. Thirteen common genes were present in four GBS-associated strains and 9 genes mapped to the LOS cluster and the ICDCCJ07001_pTet (44 kb) plasmid was mosaic in structure. Thirty-seven predicted CDS in ICDCCJ07001_pTet were homologous to genes present in three virulence-associated plasmids in Campylobacter: 81-176_pTet, pCC31 and 81-176_pVir. Comparative analysis of virulence loci and virulence-associated genes indicated that the LOS biosynthesis loci of ICDCCJ07001 belonged to type A, previously reported to be associated with cases of GBS. The polysaccharide capsular biosynthesis (CPS) loci and the flagella modification (FM) loci of ICDCCJ07001 were similar to corresponding sequences of strain 260.94 of similar serotype as strain ICDCCJ07001. Other virulence-associated genes including cadF, peb1, jlpA, cdt and ciaB were conserved between the C. jejuni strains examined

Impacts of organic and conventional crop management on diversity and activity of free-living nitrogen fixing bacteria and total bacteria are subsidiary to temporal effects

A three year field study (2007-2009) of the diversity and numbers of the total and metabolically active free-living diazotophic bacteria and total bacterial communities in organic and conventionally managed agricultural soil was conducted at the Nafferton Factorial Systems Comparison (NFSC) study, in northeast England. The result demonstrated that there was no consistent effect of either organic or conventional soil management across the three years on the diversity or quantity of either diazotrophic or total bacterial communities. However, ordination analyses carried out on data from each individual year showed that factors associated with the different fertility management measures including availability of nitrogen species, organic carbon and pH, did exert significant effects on the structure of both diazotrophic and total bacterial communities. It appeared that the dominant drivers of qualitative and quantitative changes in both communities were annual and seasonal effects. Moreover, regression analyses showed activity of both communities was significantly affected by soil temperature and climatic conditions. The diazotrophic community showed no significant change in diversity across the three years, however, the total bacterial community significantly increased in diversity year on year. Diversity was always greatest during March for both diazotrophic and total bacterial communities. Quantitative analyses using qPCR of each community indicated that metabolically active diazotrophs were highest in year 1 but the population significantly declined in year 2 before recovering somewhat in the final year. The total bacterial population in contrast increased significantly each year. Seasonal effects were less consistent in this quantitative study

Clinical Characteristics and Neonatal Outcomes of Pregnant Patients With COVID-19: A Systematic Review

Background and Objective: Coronavirus disease 2019 (COVID-19) characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created serious concerns about its potential adverse effects. There are limited data on clinical, radiological, and neonatal outcomes of pregnant women with COVID-19 pneumonia. This study aimed to assess clinical manifestations and neonatal outcomes of pregnant women with COVID-19. Methods: We conducted a systematic article search of PubMed, EMBASE, Scopus, Google Scholar, and Web of Science for studies that discussed pregnant patients with confirmed COVID-19 between January 1, 2020, and April 20, 2020, with no restriction on language. Articles were independently evaluated by two expert authors. We included all retrospective studies that reported the clinical features and outcomes of pregnant patients with COVID-19. Results: Forty-seven articles were assessed for eligibility; 13 articles met the inclusion criteria for the systematic review. Data is reported for 235 pregnant women with COVID-19. The age range of patients was 25�40 years, and the gestational age ranged from 8 to 40 weeks plus 6 days. Clinical characteristics were fever 138/235 (58.72%), cough 111/235 (47.23%), and sore throat 21/235 (8.93%). One hundred fifty six out of 235 (66.38%) pregnant women had cesarean section, and 79 (33.62%) had a vaginal delivery. All the patients showed lung abnormalities in CT scan images, and none of the patients died. Neutrophil cell count, C-reactive protein (CRP) concentration, ALT, and AST were increased but lymphocyte count and albumin levels were decreased. Amniotic fluid, neonatal throat swab, and breastmilk samples were taken to test for SARS-CoV-2 but all found negativ results. Recent published evidence showed the possibility of vertical transmission up to 30%, and neonatal death up to 2.5%. Pre-eclampsia, fetal distress, PROM, pre-mature delivery were the major complications of pregnant women with COVID-19. Conclusions: Our study findings show that the clinical, laboratory and radiological characteristics of pregnant women with COVID-19 were similar to those of the general populations. The possibility of vertical transmission cannot be ignored but C-section should not be routinely recommended anymore according to latest evidences and, in any case, decisions should be taken after proper discussion with the family. Future studies are needed to confirm or refute these findings with a larger number of sample sizes and a long-term follow-up period. © Copyright © 2020 Islam, Poly, Walther, Yang, Wang, Hsieh, Atique, Salmani, Alsinglawi, Lin, Jian and Jack Li

Novel Murine Infection Models Provide Deep Insights into the “Ménage à Trois” of Campylobacter jejuni, Microbiota and Host Innate Immunity

BACKGROUND: Although Campylobacter jejuni-infections have a high prevalence worldwide and represent a significant socioeconomic burden, it is still not well understood how C. jejuni causes intestinal inflammation. Detailed investigation of C. jejuni-mediated intestinal immunopathology is hampered by the lack of appropriate vertebrate models. In particular, mice display colonization resistance against this pathogen. METHODOLOGY/PRINCIPAL FINDINGS: To overcome these limitations we developed a novel C. jejuni-infection model using gnotobiotic mice in which the intestinal flora was eradicated by antibiotic treatment. These animals could then be permanently associated with a complete human (hfa) or murine (mfa) microbiota. After peroral infection C. jejuni colonized the gastrointestinal tract of gnotobiotic and hfa mice for six weeks, whereas mfa mice cleared the pathogen within two days. Strikingly, stable C. jejuni colonization was accompanied by a pro-inflammatory immune response indicated by increased numbers of T- and B-lymphocytes, regulatory T-cells, neutrophils and apoptotic cells, as well as increased concentrations of TNF-α, IL-6, and MCP-1 in the colon mucosa of hfa mice. Analysis of MyD88(-/-), TRIF(-/-), TLR4(-/-), and TLR9(-/-) mice revealed that TLR4- and TLR9-signaling was essential for immunopathology following C. jejuni-infection. Interestingly, C. jejuni-mutant strains deficient in formic acid metabolism and perception induced less intestinal immunopathology compared to the parental strain infection. In summary, the murine gut flora is essential for colonization resistance against C. jejuni and can be overcome by reconstitution of gnotobiotic mice with human flora. Detection of C. jejuni-LPS and -CpG-DNA by host TLR4 and TLR9, respectively, plays a key role in immunopathology. Finally, the host immune response is tightly coupled to bacterial formic acid metabolism and invasion fitness. CONCLUSION/SIGNIFICANCE: We conclude that gnotobiotic and "humanized" mice represent excellent novel C. jejuni-infection and -inflammation models and provide deep insights into the immunological and molecular interplays between C. jejuni, microbiota and innate immunity in human campylobacteriosis

The cryo-EM structure of the bacterial flagellum cap complex suggests a molecular mechanism for filament elongation

The bacterial flagellum is a remarkable molecular motor, whose primary function in bacteria is to facilitate motility through the rotation of a filament protruding from the bacterial cell. A cap complex, consisting of an oligomer of the protein FliD, is localized at the tip of the flagellum, and is essential for filament assembly, as well as adherence to surfaces in some bacteria. However, the structure of the intact cap complex, and the molecular basis for its interaction with the filament, remains elusive. Here we report the cryo-EM structure of the Campylobacter jejuni cap complex, which reveals that FliD is pentameric, with the N-terminal region of the protomer forming an extensive set of contacts across several subunits, that contribute to FliD oligomerization. We also demonstrate that the native C. jejuni flagellum filament is 11-stranded, contrary to a previously published cryo-EM structure, and propose a molecular model for the filament-cap interaction