Complete alanine scanning of the Escherichia coli RbsB ribose binding protein reveals residues important for chemoreceptor signaling and periplasmic abundance.

The Escherichia coli RbsB ribose binding protein has been used as a scaffold for predicting new ligand binding functions through in silico modeling, yet with limited success and reproducibility. In order to possibly improve the success of predictive modeling on RbsB, we study here the influence of individual residues on RbsB-mediated signaling in a near complete library of alanine-substituted RbsB mutants. Among a total of 232 tested mutants, we found 10 which no longer activated GFPmut2 reporter expression in E. coli from a ribose-RbsB hybrid receptor signaling chain, and 13 with significantly lower GFPmut2 induction than wild-type. Quantitative mass spectrometry abundance measurements of 25 mutants and wild-type RbsB in periplasmic space showed four categories of effects. Some (such as D89A) seem correctly produced and translocated but fail to be induced with ribose. Others (such as N190A) show lower induction probably as a result of less efficient production, folding and translocation. The third (such as N41A or K29A) have defects in both induction and abundance. The fourth category consists of semi-constitutive mutants with increased periplasmic abundance but maintenance of ribose induction. Our data show how RbsB modeling should include ligand-binding as well as folding, translocation and receptor binding

Guillain–Barré syndrome associated with leptomeningeal enhancement following SARS-CoV-2 infection

INTRODUCTION: Patients with coronavirus disease 2019 (COVID-19) typically present with respiratory symptoms, but little is known about the disease''s potential neurological complications.We report a case of Guillain-Barré syndrome (GBS) following a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in association with leptomeningeal enhancement. CASE PRESENTATION: A 56-year-old woman presented with recent unsteadiness and paraesthesia in both hands. Fifteen days earlier, she complained of fever, dry cough and shortness of breath. Her chest X-ray showed a lobar consolidation and PCR was positive for SARS-CoV-2; she was admitted due to mild COVID-19 pneumonia.In the first 48 hours of hospitalisation, she started to experience lumbar pain and weakness of the proximal lower extremities, progressing to bilateral facial nerve palsy, oropharyngeal weakness and severe proximal tetraparesis with cervical flexion 2/5 on the MRC scale. Full spine magnetic resonance imaging (MRI) showed a brainstem and cervical leptomeningeal enhancement. Analysis of cerebrospinal fluid (CSF) revealed albumin-cytological dissociation. Microbiological studies on CSF, including SARS-CoV-2, were negative. Nerve conduction studies were consistent with demyelinating neuropathy. She was treated with intravenous immunoglobulin, with significant neurological improvement noted over the next 2 weeks. CONCLUSION: Leptomeningeal enhancement is an atypical feature in GBS, but could be a marker of its association with SARS-CoV-2 infection

FXYD5/Dysadherin, a Biomarker of Endometrial Cancer Myometrial Invasion and Aggressiveness : Its Relationship With TGF-β1 and NF-κB Pathways

Objective: Endometrial cancer (EC) is the second most common gynecological cancer worldwide. Myometrial invasion (MI) is a key event in EC dissemination. This study aimed to evaluate FXYD5/dysadherin (FXYD5/Dys) expression in EC tissue and uterine aspirate (UA) biopsies and to assess molecular/functional changes associated with its expression in cellular models. Methods: FXYD5/Dys messenger RNA (mRNA) levels were determined in EC tissue and UA biopsies. FXYD5/Dys expression was evaluated in EC RNAseq data from The Cancer Genome Atlas (TCGA) and GENEVESTIGATOR tools. FXYD5/Dys impact on E-cadherin expression and cell behavior was assessed in EC Hec1a cells treated with transforming growth factor (TGF)-β1, stably transfected with ETV5, and transiently transfected with FXYD5/Dys small interfering RNA (siRNA) or pcDNA3-FXYD5/Dys plasmid. Results: FXYD5/Dys was associated with EC aggressiveness, finding high mRNA levels in tumors depicting MI > 50%, Grade 3, and intermediate/high risk of recurrence. FXYD5/Dys was highly expressed at the tumor invasive front compared to the superficial area. Most results were recapitulated in UA biopsies. FXYD5/Dys modulation in Hec1a cells altered cell migration/adhesion and E-cadherin expression. TGF-β1 treatment of Hec1a cells induced FXYD5/Dys expression. TCGA-UCEC RNAseq analysis revealed a positive correlation between FXYD5/Dys, TGF-β1, and plasminogen activator inhibitor (PAI)-1 mRNA levels. FXYD5/Dys induced nuclear factor (NF)-κB pathway activation in Hec1a cells. FXYD5/Dys mRNA levels positively correlated with transcriptional activation of NF-κB p65-regulated genes. Survival analysis revealed patient segregation into low- and high-risk groups, the latter depicting the highest FXYD5/Dys, PAI-1, tumor necrosis factor (TNF)-α, and TGF-β1 mRNA levels and shorter survival rates. Conclusion: FXYD5/Dys is a novel biomarker of EC progression related to TGF-β1 and NF-κB pathways that collectively promote tumor dissemination and result in poor patient prognosis

FXYD5/Dysadherin, a Biomarker of Endometrial Cancer Myometrial Invasion and Aggressiveness : Its Relationship With TGF-β1 and NF-κB Pathways

Objective: Endometrial cancer (EC) is the second most common gynecological cancer worldwide. Myometrial invasion (MI) is a key event in EC dissemination. This study aimed to evaluate FXYD5/dysadherin (FXYD5/Dys) expression in EC tissue and uterine aspirate (UA) biopsies and to assess molecular/functional changes associated with its expression in cellular models. Methods: FXYD5/Dys messenger RNA (mRNA) levels were determined in EC tissue and UA biopsies. FXYD5/Dys expression was evaluated in EC RNAseq data from The Cancer Genome Atlas (TCGA) and GENEVESTIGATOR tools. FXYD5/Dys impact on E-cadherin expression and cell behavior was assessed in EC Hec1a cells treated with transforming growth factor (TGF)-β1, stably transfected with ETV5, and transiently transfected with FXYD5/Dys small interfering RNA (siRNA) or pcDNA3-FXYD5/Dys plasmid. Results: FXYD5/Dys was associated with EC aggressiveness, finding high mRNA levels in tumors depicting MI > 50%, Grade 3, and intermediate/high risk of recurrence. FXYD5/Dys was highly expressed at the tumor invasive front compared to the superficial area. Most results were recapitulated in UA biopsies. FXYD5/Dys modulation in Hec1a cells altered cell migration/adhesion and E-cadherin expression. TGF-β1 treatment of Hec1a cells induced FXYD5/Dys expression. TCGA-UCEC RNAseq analysis revealed a positive correlation between FXYD5/Dys, TGF-β1, and plasminogen activator inhibitor (PAI)-1 mRNA levels. FXYD5/Dys induced nuclear factor (NF)-κB pathway activation in Hec1a cells. FXYD5/Dys mRNA levels positively correlated with transcriptional activation of NF-κB p65-regulated genes. Survival analysis revealed patient segregation into low- and high-risk groups, the latter depicting the highest FXYD5/Dys, PAI-1, tumor necrosis factor (TNF)-α, and TGF-β1 mRNA levels and shorter survival rates. Conclusion: FXYD5/Dys is a novel biomarker of EC progression related to TGF-β1 and NF-κB pathways that collectively promote tumor dissemination and result in poor patient prognosis

Melanesian and Asian origins of Polynesians: mtDNA and Y chromosome gradients across the Pacific

The human settlement of the Pacific Islands represents one of the most recent major migration events of mankind. Polynesians originated in Asia according to linguistic evidence or in Melanesia according to archaeological evidence. To shed light on the genetic origins of Polynesians, we investigated over 400 Polynesians from 8 island groups, in comparison with over 900 individuals from potential parental populations of Melanesia, Southeast and East Asia, and Australia, by means of Y chromosome (NRY) and mitochondrial DNA (mtDNA) markers. Overall, we classified 94.1% of Polynesian Y chromosomes and 99.8% of Polynesian mtDNAs as of either Melanesian (NRY-DNA: 65.8%, mtDNA: 6%) or Asian (NRY-DNA: 28.3%, mtDNA: 93.8%) origin, suggesting a dual genetic origin of Polynesians in agreement with the "Slow Boat" hypothesis. Our data suggest a pronounced admixture bias in Polynesians toward more Melanesian men than women, perhaps as a result of matrilocal residence in the ancestral Polynesian society. Although dating methods are consistent with somewhat similar entries of NRY/mtDNA haplogroups into Polynesia, haplotype sharing suggests an earlier appearance of Melanesian haplogroups than those from Asia. Surprisingly, we identified gradients in the frequency distribution of some NRY/mtDNA haplogroups across Polynesia and a gradual west-to-east decrease of overall NRY/mtDNA diversity, not only providing evidence for a west-to-east direction of Polynesian settlements but also suggesting that Pacific voyaging was regular rather than haphazard. We also demonstrate that Fiji played a pivotal role in the history of Polynesia: humans probably first migrated to Fiji, and subsequent settlement of Polynesia probably came from Fiji

Suppressing CMB Quadrupole with a Bounce from Contracting Phase to Inflation

Recent released WMAP data show a low value of quadrupole in the CMB temperature fluctuations, which confirms the early observations by COBE. In this paper, a scenario, in which a contracting phase is followed by an inflationary phase, is constructed. We calculate the perturbation spectrum and show that this scenario can provide a reasonable explanation for lower CMB anisotropies on large angular scales.Comment: 5 pages, 3 figure

Theoretical study of lepton events in the atmospheric neutrino experiments at SuperK

Super-Kamiokande has reported the results for the lepton events in the atmospheric neutrino experiment. These results have been presented for a 22.5kT water fiducial mass on an exposure of 1489 days, and the events are divided into sub-GeV, multi-GeV and PC events. We present a study of nuclear medium effects in the sub-GeV energy region of atmospheric neutrino events for the quasielastic scattering, incoherent and coherent pion production processes, as they give the most dominant contribution to the lepton events in this energy region. We have used the atmospheric neutrino flux given by Honda et al. These calculations have been done in the local density approximation. We take into account the effect of Pauli blocking, Fermi motion, Coulomb effect, renormalization of weak transition strengths in the nuclear medium in the case of the quasielastic reactions. The inelastic reactions leading to production of leptons along with pions is calculated in a $\Delta$- dominance model by taking into account the renormalization of $\Delta$ properties in the nuclear medium and the final state interaction effects of the outgoing pions with the residual nucleus. We present the results for the lepton events obtained in our model with and without nuclear medium effects, and compare them with the Monte Carlo predictions used in the simulation and the experimentally observed events reported by the Super-Kamiokande collaboration.Comment: 23 pages, 13 figure

Carbono orgânico dissolvido e biodisponibilidade de N e P como indicadores de qualidade do solo

Nas últimas décadas, qualidade do solo tem se tornado um tópico importante na ciência do solo. Embora esforços consideráveis tenham sido dedicados com o intuito de definir "qualidade do solo", ainda não há um conceito amplamente aceito pela comunidade cientifica. A seleção de índices qualitativos para definir qualidade do solo é uma tarefa extremamente difícil, e diversas propriedades químicas, físicas e biológicas tem sido sugeridas como potenciais indicadores. A matéria orgânica do solo está associada com processos químicos, físicos e biológicos no solo, e, portanto, é considerada um dos melhores indicadores de qualidade do solo. O manejo do solo pode influenciar significativamente a dinâmica do carbono orgânico e o ciclo de N, P, e S. Entretanto, mudanças na concentração total da matéria organica em resposta ao manejo pode ser dificil de ser detectada devido à variabilidade natural do solo. Quando comparada com a matéria orgânica total do solo, a fração mais prontamente disponível, como o carbono orgânico dissolvido (COD), é mais sensível às mudanças no manejo do solo a curto e médio prazo e, portanto, pode ser utilizada como indicador fundamental de qualidade do solo ou das alterações das condições naturais. Embora a fração dissolvida represente apenas uma pequena porção da matéria orgânica total do solo, o COD é móvel no solo e constitui uma importante fonte de C para os microorganismos, podendo facilmente refletir os efeitos de diferentes sistemas de manejo. Inúmeros métodos são utilizados para caracterizar o COD, mas os processos que influenciam sua mineralização e a disponibilidade dos elementos associado com a matéria orgânica (N, P, e S) ainda não são completamente entendidos. Pesquisas futuras devem buscar entender os processos que governam a dinâmica de nutrientes e do COD e como os mesmos afetam a qualidade do solo.Soil quality has become an important issue in soil science. Considerable attempts have been made to define soil quality, but a general concept has not yet been accepted by the scientific community. The selection of quantitative indices for soil quality is extremely difficult, and a considerable number of chemical, physical, and biochemical properties have been suggested as potential indicators of soil quality. Because soil organic matter (SOM) can be associated with different soil chemical, physical and biological processes, it has been widely considered as one of the best soil quality indicator. Land use can significantly influence dynamics of organic carbon and N, P, and S cycle. However, changes in total soil organic carbon (SOC) contents in response to land use may be difficult to detect because of the natural soil variability. In the short to medium term, biological properties and readily decomposable fractions of SOC, such as dissolved organic carbon (DOC), are much more sensitive to soil management than is SOM as a whole, and can be used as a key indicator of soil natural functions. Despite the fact that labile C accounts for a small portion of the total organic matter in the soils, DOC is the most mobile and important C-source for microorganisms, and can easily reflect the effects of land use on soil quality. Although several methods are used to characterize DOC, the factors influencing mineralization and bioavailability of elements associated with organic matter (N, P, and S) remains unclear. Future research should focus on the processes that govern DOC and nutrient dynamics and how they affect soil quality

The Atapuerca sites and the Ibeas hominids

The Atapuerca railway Trench and Ibeas sites near Burgos, Spain, are cave fillings that include a series of deposits ranging from below the Matuyama/Bruhnes reversal up to the end of Middle Pleistocene. The lowest fossil-bearing bed in the Trench contains an assemblage of large and small Mammals including Mimomys savini, Pitymys gregaloides, Pliomys episcopalis, Crocuta crocuta, Dama sp. and Megacerini; the uppermost assemblage includes Canis lupus, Lynx spelaea, Panthera (Leo) fossilis, Felis sylvestris, Equus caballus steinheimensis, E.c. germanicus, Pitymys subtenaneus, Microtus arvalis agrestis, Pliomys lenki, and also Panthera toscana, Dicerorhinus bemitoechus, Bison schoetensacki, which are equally present in the lowest level. The biostratigraphic correlation and dates of the sites are briefly discussed, as are the paleoclimatic interpretation of the Trench sequences. Stone artifacts are found in several layers; the earliest occurrences correspond to the upper beds containing Mimomys savini. A set of preserved human occupation floors has been excavated in the top fossil-bearing beds. The stone-tool assemblages of the upper levels are of upper-medial Acheulean to Charentian tradition. The rich bone breccia SH, in the Cueva Mayor-Cueva del Silo, Ibeas de Juarros, is a derived deposit, due to a mud flow that dispersed and carried the skeletons of many carnivores and humans. The taxa represented are: Vrsus deningeri (largely dominant), Panthera (Leo) fossilis, Vulpes vulpes, Homo sapiens var. Several traits of both mandibular and cranial remains are summarized. Preliminary attempts at dating suggest that the Ibeas fossil man is older than the Last Interglacial, or oxygen-isotope stage 5

The Sudbury Neutrino Observatory

The Sudbury Neutrino Observatory is a second generation water Cherenkov detector designed to determine whether the currently observed solar neutrino deficit is a result of neutrino oscillations. The detector is unique in its use of D2O as a detection medium, permitting it to make a solar model-independent test of the neutrino oscillation hypothesis by comparison of the charged- and neutral-current interaction rates. In this paper the physical properties, construction, and preliminary operation of the Sudbury Neutrino Observatory are described. Data and predicted operating parameters are provided whenever possible.Comment: 58 pages, 12 figures, submitted to Nucl. Inst. Meth. Uses elsart and epsf style files. For additional information about SNO see http://www.sno.phy.queensu.ca . This version has some new reference