Characterization of six human disease-associated inversion polymorphisms

The human genome is a highly dynamic structure that shows a wide range of genetic polymorphic variation. Unlike other types of structural variation, little is known about inversion variants within normal individuals because such events are typically balanced and are difficult to detect and analyze by standard molecular approaches. Using sequence-based, cytogenetic and genotyping approaches, we characterized six large inversion polymorphisms that map to regions associated with genomic disorders with complex segmental duplications mapping at the breakpoints. We developed a metaphase FISH-based assay to genotype inversions and analyzed the chromosomes of 27 individuals from three HapMap populations. In this subset, we find that these inversions are less frequent or absent in Asians when compared with European and Yoruban populations. Analyzing multiple individuals from outgroup species of great apes, we show that most of these large inversion polymorphisms are specific to the human lineage with two exceptions, 17q21.31 and 8p23 inversions, which are found to be similarly polymorphic in other great ape species and where the inverted allele represents the ancestral state. Investigating linkage disequilibrium relationships with genotyped SNPs, we provide evidence that most of these inversions appear to have arisen on at least two different haplotype backgrounds. In these cases, discovery and genotyping methods based on SNPs may be confounded and molecular cytogenetics remains the only method to genotype these inversions

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Hydrolysis of soybean isoflavones by Debaryomyces hansenii UFV-1 immobilised cells and free β-glucosidase

An intracellular β-glucosidase from Debaryomyces hansenii UFV-1 was produced in an YP medium with cellobiose as the carbon source. This enzyme was purified, characterised and presented a Mr of 65.15 kDa. Yeast cells containing the intracellular β-glucosidase were immobilised in calcium alginate. The free β-glucosidase and immobilised cells containing the enzyme presented optima values of pH and temperature of 6.0 and 45 °C and 5.5 and 50 °C, respectively. The free enzyme maintained 62% and 47% of its original activity after 90 days at 4 °C and after 15 days at room temperature, respectively. The immobilisation process resulted in higher enzyme thermostability at 45 and 50 °C. Soy molasses treatment with the free enzyme and the immobilised cells containing β-glucosidase, for 2 h at 40 °C, promoted efficient hydrolysis of isoflavone glicosides to their aglycon forms. The results suggest that this enzyme could be used in the food industry, in the free or immobilised forms, for a safe and efficient process to hydrolyse isoflavone glycosides in soy molasses

Direct ethanol production from glucose, xylose and sugarcane bagasse by the corn endophytic fungi Fusarium verticillioides and Acremonium zeae

Production of ethanol with two corn endophytic fungi, Fusarium verticillioides and Acremonium zeae, was studied. The yield of ethanol from glucose, xylose and a mixture of both sugars were 0.47, 0.46 and 0.50 g/g ethanol/sugar for F. verticillioides and 0.37, 0.39 and 0.48 g/g ethanol/sugar for A. zeae. Both fungi were able to co-ferment glucose and xylose. Ethanol production from 40 g/L of pre-treated sugarcane bagasse was 4.6 and 3.9 g/L for F. verticillioides and A. zeae, respectively, yielding 0.31 g/g of ethanol per consumed sugar. Both fungi studied were capable of co-fermenting glucose and xylose at high yields. Moreover, they were able to produce ethanol directly from lignocellulosic biomass, demonstrating to be suitable microorganisms for consolidated bioprocessing

Characteristics of free endoglucanase and glycosidases multienzyme complex from Fusarium verticillioides

A novel multienzyme complex, E1 C , and a free endoglucanase, E2 (GH5), from Fusarium verticillioides were purified. The E1 C contained two endoglucanases (GH6 and GH10), one cellobiohydrolase (GH7) and one xylanase (GH10). Maximum activity was observed at 80 °C for both enzymes and they were thermostable at 50 and 60 °C. The activation energies for E1 C and E2 were 21.3 and 27.5 kJ/mol, respectively. The K M for E1 C was 10.25 g/L while for E2 was 6.58 g/L. Both E1 C and E2 were activated by Mn 2+ and CoCl 2 while they were inhibited by SDS, CuSO 4 , FeCl 3 , AgNO 4 , ZnSO 4 and HgCl 2 . E1 C and E2 presented endo-b-1,3–1,4-glucanase activity. E1 C presented crescent activity towards cellopentaose, cellotetraose and cellotriose. E2 hydrolyzed the substrates cellopentaose, cellotetraose and cellotriose with the same efficiency. E1 C showed a higher stability and a better hydrolysis performance than E2, suggesting advantages resulting from the physical interaction between proteins

White Matter Hyperintensities and Hippocampal Atrophy in Relation to Cognition: The 90+ Study

OBJECTIVES: To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old. DESIGN: Ongoing longitudinal study. SETTING: In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017. PARTICIPANTS: Individuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment). MEASUREMENTS: Cognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education. RESULTS: Mean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline. CONCLUSION: We show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827–1834, 2019

Optimization of Endoglucanase and Xylanase activities from fusarium verticillioides for simultaneous saccharification and fermentation of sugarcane bagasse

Enzymatic hydrolysis is an important but expensive step in the production of ethanol from biomass. Thus, the production of efficient enzymatic cocktails is of great interest for this biotechnological application. The production of endoglucanase and xylanase activites from F. verticillioides were optimized in a factorial design (25) followed by a CCDR design. Endoglucanase and xylanase activities increased from 2.8 to 8.0 U/mL and from 13.4 to 114 U/mL, respectively. The optimal pH and temperature were determined for endoglucanase (5.6, 80 °C), cellobiase (5.6, 60 °C), FPase (6.0, 55 °C) and xylanase (7.0, 50 °C). The optimized crude extract was applied in saccharification and fermentation of sugarcane bagasse from which 9.7 g/L of ethanol was produced at an ethanol/biomass yield of 0.19

Sexual Orientation Differences in Complementary Health Approaches Among Young Adults in the United States

PURPOSE: Lesbian, gay, and bisexual (LGB) young adults experience a wide range of health disparities, compared to heterosexuals. However, LGBs also experience many barriers to conventional healthcare, including social stigma, lack of LGB-specific knowledge among providers, and lower rates of health insurance coverage, which may limit utilization of traditional health services. Complementary health approaches (CHA) may represent an alternative to conventional care, but very little is currently known about CHA use in this population. We examined whether and how LGB young adults differed from heterosexual young adults in use of CHA. METHODS: Data were from Wave III of the National Longitudinal Study of Adolescent to Adult Health (2001-02). Fifteen types of CHA were considered. Descriptive and bivariate statistics were computed using design-based F-tests and logistic regression was used. Analyses were weighted and gender-stratified. RESULTS: Almost 46% of gay/bisexual men used CHA in the past 12 months versus 26% of heterosexual men (p<0.001) and 50% of lesbian/bisexual women versus 30% of heterosexual women (p<0.001). LGBs also differed significantly on demographics, access to conventional care, and health behaviors. Multivariate results showed higher odds of CHA among LGBs relative to heterosexuals (AOR = 2.37 for men, AOR = 1.98 for women, both p<0.001). CONCLUSIONS: This is the first study to systematically demonstrate sexual orientation differences in CHA in a nationally representative sample of young adults. Public health wellness initiatives for sexual minorities should include evidence-based CHA in addition to traditional health services