Transcriptional regulation of the glucoamylase-encoding gene under endoplasmic reticulum stress in Aspergillus niger

The ability of many filamentous fungi, such as Aspergillus niger, to secret a high level of homologous proteins has led to their consideration as hosts for the production of heterologous proteins. However, the levels of some secreted heterologous proteins have often been low. Although many strategies have been developed to improve the level of secreted heterologous proteins, further studies into the remaining bottlenecks are required. One common strategy used to improve secreted protein production from filamentous fungi is to express the target protein under the control of a highly-induced native promoter. One major bottleneck in the secretion of heterologous proteins is caused by the folding of proteins within the lumen of the endoplasmic reticulum (ER). Recent studies have shown that expressing some heterologous proteins could subject A. niger to ER-stress. In this study, A. niger was subjected to different environmental conditions and ER stress responses were examined under each of these environmental conditions to further investigate the regulation of the gene encoding glucoamylase (glaA). Treating A. niger with dithiothreitol (OTT), a reducing agent that causes the formation of unfolded proteins, caused the down-regulation of transcription of the glaA but not the gene encoding the non-secreted protein y-actin. The OTT-treated fungal cells also showed evidence of induction of the UPR because expression of bipA was up-regulated and splicing of hacA, the gene encoding the transcription factor responsible for induction of the Unfolded Protein Response (UPR), occurs allowing the production of an active HacA protein. This is the first study to show clearly by nuclear run-on studies that the transcriptional down-regulation effect occurs at the level of transcription, rather than mRNA stability, and is found to be mediated through the promoter of the glaA gene (PglaA) in a region more than 1.192 kb upstream of the translational start. As a preliminary attempt to investigate if the transcriptional downregulation effect was mediated through HacA (i.e. part of the UPR), the ER stress was induced through antisense technology to lower the level of POI in the ER of A. niger. Although the transcription of glaA was attenuated in that strain of A. niger, UPR was not evident, suggesting that the transcriptional down-regulation mechanism is controlled differently from the UPR. Furthermore, activation of the ER-Associated Degradation (ERAO) mechanism in OTT-treated A. niger cultures was demonstrated by detecting transcriptional up-regulation of the putative gene encoding the RpnG, a homologue of the yeast Rpn7p subunit of the 26S proteasome

Geoquímica del rango volcánico alcalino del eoceno medio-superior, parte sur de las montañas centrales de Alborz, norte de Irán

The Ziaran volcanic Belt (ZVB), North of Iran contains a number of intra-continental alkaline volcanic range situated on South part of central Alborz Mountains, formed along the localized extensional basins developed in relation with the compressional regime of Eocene. The mid-upper Eocene volcanic suite comprises the extracted melt products of adiabatic decompression melting of the mantle that are represented by small volume intra-continental plate volcanic rocks of alkaline volcanism and their evaluated Rocks with compositions representative of mantle-derived, primary (or near-primary) melts. Trace element patterns with significant enrichment in LILE, HFSE and REEs, relative to Primitive Mantle. Chondrite-normalized of rare earth elements and enrichment in incompatible elements and their element ratios (e. g. LREE/HREE, MREE/HREE, LREE/MREE) shown these element modelling indicates that the magmas were generated by comparably variable degrees of partial melting of garnet lherzolite and a heterogeneous asthenospheric, OIB mantle sources.El cinturón volcánico de Ziaran (ZVB), al norte de Irán, contiene una serie de cordilleras volcánicas alcalinas intracontinentales situadas en la parte sur de las montañas centrales de Alborz, formadas a lo largo de las cuencas extensionales localizadas desarrolladas en relación con el régimen de compresión del Eoceno. La suite volcánica del Eoceno medio superior comprende los productos de fusión extraídos de la fusión por descompresión adiabática del manto que están representados por rocas volcánicas de placa intracontinental de pequeño volumen de vulcanismo alcalino y sus rocas evaluadas con composiciones representativas de las rocas derivadas del manto, primarias (o cercanas). -primaria) se derrite. Patrones de oligoelementos con enriquecimiento significativo en LILE, HFSE y REE, en relación con Primitive Mantle. Condrita normalizada de elementos de tierras raras y enriquecimiento en elementos incompatibles y sus proporciones de elementos (por ejemplo, LREE / HREE, MREE / HREE, LREE / MREE) que muestra el modelado de estos elementos indica que los magmas se generaron por grados comparativamente variables de fusión parcial de granate lherzolita y fuentes de manto OIB astenosféricas heterogéneas

Geoquímica del rango volcánico alcalino del eoceno medio-superior, parte sur de las montañas centrales de Alborz, norte de Irán

The Ziaran volcanic Belt (ZVB), North of Iran contains a number of intra-continental alkaline volcanic range situated on South part of central Alborz Mountains, formed along the localized extensional basins developed in relation with the compressional regime of Eocene. The mid-upper Eocene volcanic suite comprises the extracted melt products of adiabatic decompression melting of the mantle that are represented by small volume intra-continental plate volcanic rocks of alkaline volcanism and their evaluated Rocks with compositions representative of mantle-derived, primary (or near-primary) melts. Trace element patterns with significant enrichment in LILE, HFSE and REEs, relative to Primitive Mantle. Chondrite-normalized of rare earth elements and enrichment in incompatible elements and their element ratios (e. g. LREE/HREE, MREE/HREE, LREE/MREE) shown these element modelling indicates that the magmas were generated by comparably variable degrees of partial melting of garnet lherzolite and a heterogeneous asthenospheric, OIB mantle sources.El cinturón volcánico de Ziaran (ZVB), al norte de Irán, contiene una serie de cordilleras volcánicas alcalinas intracontinentales situadas en la parte sur de las montañas centrales de Alborz, formadas a lo largo de las cuencas extensionales localizadas desarrolladas en relación con el régimen de compresión del Eoceno. La suite volcánica del Eoceno medio superior comprende los productos de fusión extraídos de la fusión por descompresión adiabática del manto que están representados por rocas volcánicas de placa intracontinental de pequeño volumen de vulcanismo alcalino y sus rocas evaluadas con composiciones representativas de las rocas derivadas del manto, primarias (o cercanas). -primaria) se derrite. Patrones de oligoelementos con enriquecimiento significativo en LILE, HFSE y REE, en relación con Primitive Mantle. Condrita normalizada de elementos de tierras raras y enriquecimiento en elementos incompatibles y sus proporciones de elementos (por ejemplo, LREE / HREE, MREE / HREE, LREE / MREE) que muestra el modelado de estos elementos indica que los magmas se generaron por grados comparativamente variables de fusión parcial de granate lherzolita y fuentes de manto OIB astenosféricas heterogéneas

The Petrology of Ziyran Volcanic Belt (ZVB) Eocene Volcanic Rocks

The Ziyaran Volcanic Belt (ZVB) is located in the southern part of central Alborz and in the Ziyaran area. The geology of this layer includes various kinds of stone units. In the north, they are the reminder of Cenozoic, quaternary deposits, and in the western part, the exposure stone units are mostly Precambrian and Paleozoic deposits and in the south-eastern part of the studied area, the stones belong to the Mesozoic era and specifically, the sediments belong to the Jurassic era are exposed. Also, the basic volcanic rocks that belong to the Eocene period are located in the Ziyaran area, in the western part of Taleqan County and in the Alborz state. This study aimed to evaluate the petrology of Ziyaran Volcanic Belt (ZVB) Eocene volcanic rocks. For this purpose, which is mostly focused on the study of Cretaceous stones in the central Alborz zone, sampling of the stones in the intended area was performed with the survey and field methods and for 120 samples. After the preparation of the thin layer from the well and without alteration samples, they were examined with petrography and petrology tests. The results of the petrology studies of the volcanic rocks of the Ziyaran area expressed that the basic volcanic rocks in the intermediate area with the intermediate- upper chemical composition of Eocene Alkaline Phosphatase (ALP) located in the central zone of Alborz heights, with lithology composition of Alkali olivine basalts and Andesite

Geoquímica del rango volcánico alcalino del eoceno medio-superior, parte sur de las montañas centrales de Alborz, norte de Irán

El cinturón volcánico de Ziaran (ZVB), al norte de Irán, contiene una serie de cordilleras volcánicas alcalinas intracontinentales situadas en la parte sur de las montañas centrales de Alborz, formadas a lo largo de las cuencas extensionales localizadas desarrolladas en relación con el régimen de compresión del Eoceno. La suite volcánica del Eoceno medio superior comprende los productos de fusión extraídos de la fusión por descompresión adiabática del manto que están representados por rocas volcánicas de placa intracontinental de pequeño volumen de vulcanismo alcalino y sus rocas evaluadas con composiciones representativas de las rocas derivadas del manto, primarias (o cercanas). -primaria) se derrite. Patrones de oligoelementos con enriquecimiento significativo en LILE, HFSE y REE, en relación con Primitive Mantle. Condrita normalizada de elementos de tierras raras y enriquecimiento en elementos incompatibles y sus proporciones de elementos (por ejemplo, LREE / HREE, MREE / HREE, LREE / MREE) que muestra el modelado de estos elementos indica que los magmas se generaron por grados comparativamente variables de fusión parcial de granate lherzolita y fuentes de manto OIB astenosféricas heterogéneas

The Petrology of Ziyran Volcanic Belt (ZVB) Eocene Volcanic Rocks

The Ziyaran Volcanic Belt (ZVB) is located in the southern part of central Alborz and in the Ziyaran area. The geology of this layer includes various kinds of stone units. In the north, they are the reminder of Cenozoic, quaternary deposits, and in the western part, the exposure stone units are mostly Precambrian and Paleozoic deposits and in the south-eastern part of the studied area, the stones belong to the Mesozoic era and specifically, the sediments belong to the Jurassic era are exposed. Also, the basic volcanic rocks that belong to the Eocene period are located in the Ziyaran area, in the western part of Taleqan County and in the Alborz state. This study aimed to evaluate the petrology of Ziyaran Volcanic Belt (ZVB) Eocene volcanic rocks. For this purpose, which is mostly focused on the study of Cretaceous stones in the central Alborz zone, sampling of the stones in the intended area was performed with the survey and field methods and for 120 samples. After the preparation of the thin layer from the well and without alteration samples, they were examined with petrography and petrology tests. The results of the petrology studies of the volcanic rocks of the Ziyaran area expressed that the basic volcanic rocks in the intermediate area with the intermediate- upper chemical composition of Eocene Alkaline Phosphatase (ALP) located in the central zone of Alborz heights, with lithology composition of Alkali olivine basalts and Andesite

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe