Zonation of glucokinase in rat liver changes during postnatal development

AbstractIn the liver many metabolic pathways are preferentially localized in different zones of the acinus. It is assumed that this zonation allows an efficient adaptation to different states of nutrition, because alternative pathways can be regulated independently. It is reported that the rate limiting enzyme for the glycolytic pathway, glucokinase (EC 2.7.1.2), is predominantly located in the pericentral zone. The gene expression of glucokinase is induced to a maximum level after a carbohydrate-rich diet. In starved or diabetic rats glucokinase gene expression is barely detectable. In postnatal development glucokinase is induced to significant levels only from day 14 onwards. The distribution of the glucokinase protein in the rat liver lobule in the first 4 weeks of postnatal life was investigated by immunohistochemistry and compared to the distribution observed in adult rats. In adult rats considerably high levels of glucokinase are measureable as shown by immunoblotting utilizing a monospecific antibody and a photometric assay of glucokinase enzyme activity, respectively. Immunohistochemically the hepatic glucokinase protein is detected in the perivenous area. During postnatal development, the quantities of hepatic glucokinase protein and glucokinase enzyme activity start to increase significantly from day 15 onwards. Subsequently, glucokinase levels rise further until day 29. In contrast to the results obtained by immunoblotting, glucokinase is already detectable in some liver cells in sections from 6-day-old rats by immunohistochemistry. The liver lobule structure at this age is not completely developed, therefore it is not possible to definitely assign these cells to periportal or pericentral areas. At day 10 post partum the number of glucokinase expressing cells, which appear to be localized preferentially in the periportal zone, increases. In agreement with the immunoblotting, an immense increase in glucokinase activity was observed at day 14. The periportal zonation, clearly detectable at this time, remains stable until day 24. In sections from 29-day-old rats the periportal zonation begins to change into a more homogeneous pattern with a slight preference for periportal areas. The observed appearance of the periportal zonation of glucokinase during neonatal development is obviously in contrast to the perivenous expression of glucokinase in adult rats

Doubly Differential Electron-Emission Spectra in Single and Multiple Ionization of Noble-Gas Atoms by Fast Highly-Charged-Ion Impact

Low-energy electron emission spectra are studied in collisions of 3.6 MeV/amu Au53+ ions with neon and argon atoms for well-defined degrees of target ionization. We calculate doubly differential cross sections as functions of the recoil-ion charge state in the continuum-distorted-wave with eikonal initial-state approximation using a binomial analysis of the total and differential ionization probabilities, and compare them with the present and with previously published experimental data. Very good agreement is found for the single-ionization spectra and for double ionization of neon, while some discrepancies are observed in the spectra for double and triple ionization of argon

Systematic Analysis of Double-Ionization Dynamics Based on Four-Body Dalitz Plots

We report on an experimental and theoretical systematic study of double ionization of helium by ion impact in terms of four-particle Dalitz plots. Several collision systems covering abroad range of perturbation parameters η (projectile charge to speed ratio) were investigated. With increasing η we observe a systematic trend from features, characteristic to correlated double-ionization mechanisms, to signatures of higher-order processes not requiring electron-electron correlations [the mechanism called two-step-two projectile-electron interaction (TS-2)]. The data for the largest η can qualitatively be amazingly well described by a simple model only including the TS-2 mechanism

Spezielle Therapiesituationen beim metastasierten kolorektalen Karzinom

Specific Treatment Situations in Metastatic Colorectal Cancer As far as the management of primary resectable liver metastases is concerned, three approaches are currently competing with each other: surgery alone, surgery with pre- and postoperative chemotherapy, and surgery with postoperative chemotherapy alone. The core of the argument for pre- and postoperative chemotherapy in these patients is the European Organisation for Research and Treatment of Cancer (EORTC) 40983 study, which concluded that, in comparison with surgery alone, perioperative chemotherapy improved the 3-year progression-free survival (PFS) by 7 months. In contrast to this, there are two smaller studies - at a somewhat lower strength of evidence - indicating that adjuvant chemotherapy extends PFS by 9.1 months compared with surgery alone. In Germany, the adjuvant approach continues to be favored in many places; this can also be seen in the formulation of the S3 guideline. In patients with unresectable liver metastases - with the associated difficulty of classification due to the lack of clear and definitive criteria preoperative systemic therapy to induce `conversion' is indicated, in order to allow secondary resection. In KRAS wild-type tumors, high response rates ( in terms of a reduction in size of the metastases, such as according to RECIST ( Response Evaluation Criteria in Solid Tumors)) and a high conversion rate are achieved using a cetuximab/chemotherapy combination. Triple chemotherapy combinations with 5-fluorouracil (5-FU), oxaliplatin and irinotecan also produce high response rates. Bevacizumab/chemotherapy combinations have led to a high number of complete and partial pathohistological remissions in phase II studies; these seem to correlate with long survival times. In the absence of long-term survival data, it therefore seems to remain unclear as to what is the best parameter to use in order to assess the success of preoperative treatment. Lung metastases, too, or local peritoneal carcinomatosis can nowadays be operated on in selected patients with a good prospect of long-term remission or even cure. The surgery should, however, generally only be carried out in experienced centers, especially in the case of peritoneal carcinomatosis. For synchronous metastasization, the appropriate management depends on the size and extent of liver metastases and of the primary tumor. Small, peripherally lying and safely resectable liver metastases can be removed before or at the same time as the primary tumor, especially if a hemicolectomy is being carried out. If the metastases are unresectable and there is no bleeding or stenosis, the primary tumor can also be left in situ and systemic chemotherapy can be carried out first. However, it should be borne in mind that, according to current data, palliative resection of the primary tumor combined with systemic therapy leads to longer overall survival than does chemotherapy alone. Whether resection or chemotherapy should be done first therefore depends on the patient's clinical situation

Ermittlung der existenzsichernden Bedarfe für die Kosten der Unterkunft und Heizung in der Grundsicherung für Arbeitsuchende nach dem Zweiten Buch Sozialgesetzbuch (SGB II) und in der Sozialhilfe nach dem Zwölften Buch Sozialgesetzbuch (SGB XII): Endbericht mit Materialband vom 30.11.2016

Die vorliegende Studie befasst sich mit der Ermittlung existenzsichernder Bedarfe der Unterkunft und Heizung für Bedarfs- und Einstandsgemeinschaften nach SGB II und SGB XII. Zum einen untersucht sie auf der Grundlage einer bundesweiten Kommunalbefragung, zwölf Fallstudien sowie zwanzig Expertengesprächen die aktuelle Umsetzungspraxis. Es werden unterschiedliche Verfahrensweisen der Grundsicherungs- und Sozialhilfeträger unter Berücksichtigung der wohnungsmarktlichen Rahmbedingungen analysiert und zentrale Herausforderungen und Probleme der Umsetzung diskutiert. Hier zeigt sich eine Vielfalt an Umsetzungswegen, die letztlich durch normative Entscheidungsspielräume auf kommunaler Ebene geprägt und weniger durch unterschiedliche Wohnungsmarktkontexte begründet ist. Zum anderen werden in der Studie mit dem Ziel einer existenzsichernden Bedarfsdeckung unterschiedliche Verfahren entwickelt, mit Hilfe derer mögliche Mietobergrenzen berechnet werden. Dabei differenziert die Studie zwischen drei grundlegenden Bemessungsansätzen, die im Wesentlichen auf der Abbildung der Wohnkosten einer definierten Referenzgruppe, den ortsüblichen Miete eines bestimmten Wohnstandards oder den Kosten für die Neuanmietung einer ausreichenden Menge von Wohnraum basieren. Verknüpft mit den verschiedenen Ansätzen sind unterschiedliche Datengrundlagen und Berechnungsschritte. Die Vergleichsberechnung in den zwölf Fallstudien und 878 deutschen Mittelbereichen zeigt im Ergebnis deutliche Unterschiede. Abschließend werden unterschiedliche Wege der Weiterentwicklung der rechtlichen Rahmensetzung diskutiert. Hier werden Möglichkeiten der Bedarfsbemessung durch den Bund, die durch die aktuelle Datenlage beschränkt werden, und Empfehlungen bezüglich einzelner Verfahrensschritte der Bemessung beschrieben.The study seeks to appraise the rent benefit level necessary to meet welfare recipients’ basic need for housing and heating. First, it examines the actual practice at a local level based on a nationwide survey, twelve case studies and twenty interviews with experts. The study analyses the different approaches of welfare authorities while considering regional housing market conditions. The crucial challenges and problems regarding implementation are also discussed, revealing that there are a variety of implementation paths. These are determined by normative decisions at a local level rather than different housing market contexts. Second, the study develops different approaches with the goal of calculating potential limits to ensure that the rent benefit level can meet the basic requirements for housing and heating. Here, the study differentiates between three basic assessment options based on: the housing costs of a defined reference group of low-income recipients, the usual local rent for a simple dwelling or the cost that allows for access to a share of the rental housing market that satisfies demand. Different data sources and calculation steps are linked with these three basic assessment options. A comparative calculation regarding the twelve case studies and the 878 German Mittelbereiche (geographical regions served by central places of the second out of four levels of importance) shows very different results. Finally, the study discusses different ways of developing the legal framework. This includes options for determining the rent benefit level by the federal government, that are constrained by the current lack of data, and suggestions referring to the different steps of determining the level by the local authorities

Показатели токсичности промышленных отходов

Безотходное производство - новая тенденция в промышленности всего мира. Продукция, получаемая из вторсырья, считается экологичной. Данное направление приветствуется в обществе. Но прежде чем приступить к переработке любой отход проходит оценку на пригодность для дальнейшего использования и токсичность. В зависимости от класса отхода применяется инструментальные методы (химические, физические и физико-химические) или биологические (биоиндикация, биотетирование).Wasteless production is a new trend in the industry of the whole world. Products derived from recyclables are considered environmentally friendly. This direction is becoming popular. Before recycling wastes pass the toxicity assessment. Permission or renouncemen will be issued after verification. Depending on the class of waste, instrumental methods (chemical, physical and physico-chemical), biological methods (bioindication, biotesting) are used

Sensors in the stream: the high-frequency wave of the present

New scientific understanding is catalysed by novel technologies that enhance measurement precision, resolution or type, and that provide new tools to test and develop theory. Over the last 50 years, technology has transformed the hydrologic sciences by enabling direct measurements of watershed fluxes (evapotranspiration, streamflow) at time scales and spatial extents aligned with variation in physical drivers. High frequency water quality measurements, increasingly obtained by in-situ water quality sensors, are extending that transformation. Widely available sensors for some physical (temperature) and chemical (conductivity, dissolved oxygen) attributes have become integral to aquatic science, and emerging sensors for nutrients, dissolved CO2, turbidity, algal pigments, and dissolved organic matter are now enabling observations of watersheds and streams at timescales commensurate with their fundamental hydrological, energetic, elemental, and biological drivers. Here we synthesize insights from emerging technologies across a suite of applications, and envision future advances, enabled by sensors, in our ability to understand, predict, and restore watershed and stream systems

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

Nanomaterials for Neural Interfaces

This review focuses on the application of nanomaterials for neural interfacing. The junction between nanotechnology and neural tissues can be particularly worthy of scientific attention for several reasons: (i) Neural cells are electroactive, and the electronic properties of nanostructures can be tailored to match the charge transport requirements of electrical cellular interfacing. (ii) The unique mechanical and chemical properties of nanomaterials are critical for integration with neural tissue as long-term implants. (iii) Solutions to many critical problems in neural biology/medicine are limited by the availability of specialized materials. (iv) Neuronal stimulation is needed for a variety of common and severe health problems. This confluence of need, accumulated expertise, and potential impact on the well-being of people suggests the potential of nanomaterials to revolutionize the field of neural interfacing. In this review, we begin with foundational topics, such as the current status of neural electrode (NE) technology, the key challenges facing the practical utilization of NEs, and the potential advantages of nanostructures as components of chronic implants. After that the detailed account of toxicology and biocompatibility of nanomaterials in respect to neural tissues is given. Next, we cover a variety of specific applications of nanoengineered devices, including drug delivery, imaging, topographic patterning, electrode design, nanoscale transistors for high-resolution neural interfacing, and photoactivated interfaces. We also critically evaluate the specific properties of particular nanomaterials—including nanoparticles, nanowires, and carbon nanotubes—that can be taken advantage of in neuroprosthetic devices. The most promising future areas of research and practical device engineering are discussed as a conclusion to the review.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64336/1/3970_ftp.pd

Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.

Aims: Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. Methods and results: We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Conclusions: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria