Characterization of novel glomerular proteins : role in physiology and disease

Glomerular damage accounts for the majority of chronic kidney disease cases, the prevalence of which is dramatically escalating worldwide, mainly due to increase in diabetes and associated nephropathy. The costs for treatment of CKD represent an enormous burden to the health care system. Chronic kidney disease frequently progresses to end-stage renal disease with the only curative treatment options today are lifelong dialysis or kidney transplantation. In order to better understand and treat glomerular disease before it has reached this irreversible stage, it is imperative to understand the cell biology and physiology of the glomerulus including delineation of the molecular make-up of glomerular filtration barrier. This barrier constitutes the endothelial cells of the glomerular capillaries with its bound surface layer of a carbohydrate-rich meshwork (glycocalyx), the glomerular basement membrane, and the podocytes with the sub podocytes space and the attached slit diaphragm spanning between neighboring and interdigitating foot processes. Even though the concerted interplay of all layers of the glomerular filtration barrier is important for the ultra-filtration of the plasma, the podocytes and their injuries have recently been acknowledged as the major culprit of glomerular disease. In this thesis work, I describe two novel podocyte specific proteins, TDRD5 and RHPN1, which we show in vivo to be important for the integrity of the glomerular filtration barrier. TDRD5 has previously been considered a male germ cell line specific protein important for retro transposon silencing and spermiogenesis in mice. Here I show that it is expressed in mouse and human podocytes and is enriched in the zebrafish glomerulus. By using the in vivo morpholino knock down technique in zebrafish larvae it was demonstrated that TDRD5 expression is required for the proper formation of the zebrafish pronephros. RHPN1 is a RHOA binding protein which functions as an attenuator of the polymerization of actin stress fibers by regulating the phosphorylation of nonmuscle myosin II regulatory light chain through RHOA downstream effectors. Deletion of the Rhpn1 gene leads to neonatal albuminuria and glomerular basement membrane abnormality. The phenotype was characterized. As a part of efforts to elucidate expression signatures of glomerular diseases, the global glomeruli expression pattern of Adriamycin treated nephrotic mice was analyzed by RNA sequencing. The Adriamycin induced nephropathy mouse model mimics the human disease focal segmental glomerular sclerosis which constitutes one of the main causes of chronic kidney disease. The diabetic nephropathy associated single nucleotide polymorphism 3q locus was shown in our work to be a remote cis-acting variant differentially regulating glomerular NCK1 expression, implicating an important role for glomerular NCK1 in diabetic nephropathy pathogenesis

Communicative coworkership

Communicative coworkership is an area with great potential for both organizations and communicators. Communicative coworkership is also an area where there is a clear link between the core operation and the communication of the organization. It is fairly easy to demonstrate the value of communicative coworkership for an organisation, for example in terms of crisis aversion, innovation, listening, learning, branding, trust and other aspects that have an important strategic value for organisations in general.In this report, we present previous research on communicative coworkership and propose a definition of the concept. We provide a model that shows three areas of responsibility for communicative coworkership. In addition, we discuss obstacles to communicative coworkership and the support that the organization can provide to employees.In the final discussion, we present the wheel of communicative coworkership with six factors that must exist in order to realise the idea of communicative coworkership: (1) sensemaking approach to communication, (2) communicative leadership, (3) decentralised organizational philosophy, (4) open communication climate, (5) internal trust and (6) identification with the organization

Vad styr sortimentet hos svenska perennaodlare?

The purpose of this study is to clarify the most important factors that affect Swedish perennial growers when designing their assortment. The study describes how herbaceous perennials are produced in Sweden today and try to give an answer to the question how growing method and choice of assortment are affecting the possibilities of Swedish producers to compete on the market. Seven perennial growers in the southern and western parts of Sweden have been interviewed about their production methods and on what basis they design the assortment of perennials. During the interviews five factors seem to be the most important when the growers choose which species to grow – profitability, the characteristics of the species, the sales channel/customer, the growing environment/growing facility and the grower's interest and knowledge. It is often a combination of these five factors deciding if a cultivar will be grown or not.Detta examensarbete syftar till att belysa hur svenska perennaodlare fattar beslut om utformningen av det sortiment av örtartade perenner som ska odlas i företaget. I arbetet presenteras det sätt på vilket perenner odlas i Sverige idag och frågor som besvaras i arbetet är hur odlingssättet och utformningen av sortimentet påverkar den svenska perennaodlingens konkurrensförmåga. Sju perennaodlare i södra och västra Götaland har intervjuats om sin odling och vad som styr deras val av sortiment idag. Under intervjuerna har det utkristalliserat sig fem faktorer som styr odlarna i deras utformning av sortiment – lönsamhet, sortegenskaper, försäljningskanal/ kundkategori, odlingssystem/odlingsfaciliteter och odlarens intresse och kunskaper. Det är oftast en kombination av dessa faktorer som avgör om en sort tas in eller ur sortimentet

Säkra konstruktioner och anvisningar för golvbrunnar i träbjälklag

Leakage at the floor drain is the biggest cause of moisture damage in bathrooms today. Wooden joists are the most common type of joist structure in houses and because of wood being a moisture sensitive material, moisture damage at the floor drain can lead to big problems. The purpose of this paper was to find out the most common reasons to why moisture damages occur at floor drains installed in wooden joists, so that assembly methods can be improved and moisture damages can be prevented. TräGuiden is a webpage were instructions and advices are available to both individuals and businesses. In the section Golvbrunn i träbjälklag there is a general information on how the joists should be reinforced before the assembly of the floor drain. The purpose was to develop this chapter on TräGuidens website so that updated, educational and more detailed information can reach the public. Conversations with experienced operators in the industry of floor drains and wet rooms were conducted to get their view of how big the problem with moisture damages at the floor drains are and how they work to prevent this. They believed that the wall adjacent drains are the future and that the waterproof membranes together with incorrect assembly are the biggest reasons for moisture damages occurring at the floor drain. Insurance cases of moisture damages at the floor drain were collected at Länsförsäkringar in Skåne and were summarized into tables and charts. The result shows that leakage at the waterproof membranes connection to the floor drain is the biggest risk for moisture damages to occur at the floor drain. Factors such as the clamping ring is not fulfilling its function and that the floor drain is incorrectly mounted, are also common risks. In a greater extent the combinations of different causes of damage are a risk that will lead to the occurrence of moisture damages. A new proposal to TräGuiden was developed. The new version contains descriptions, comments and references to industry associations. It gives an overview of the assembly from the beginning to the end, were all the steps in the mounting process has been included

Gårdsslakteri

Eftersom vi har ett eget stort intresse för djurvälfärdsfrågor och produktion av livsmedel med hög kvalitet har vi valt att fördjupa våra kunskaper inom gårdsslakt. I en tid där vi går mot allt färre stora slakterier, som leder till långa transporter för djuren och resulterar i ökad stress och skaderisk, så känns detta extra aktuellt. Vi har därför sammanfattat det vi tycker är viktigast att tänka på för den som går i tankarna att starta ett eget slakteri. Det man bör börjar med är att kontakta kommunen för bygganmälan och söka byggnadslov, där skall man även söka miljötillstånd för sin verksamhet. Därefter vänder man sig till livsmedelsverket med sin verksamhetsbeskrivning och planritning för att få tillstånd att producera livsmedel. Jordbruksverket kontaktas för att få ett produktionsplatsnummer. All slakteriverksamhet är noga reglerad av lagar och förordningar som man hittar på livsmedelsverkets och jordbruksverkets hemsidor. Vid planering av byggnaden är det viktigt att tänka på varu- och personalflöden så att det finns möjlighet att hålla isär oren och ren hantering. Djur, djurkroppar och personal skall utan att korsa varandras vägar kunna gå från oren till ren zon. Slaktlokalens golv, väggar och tak skall vara av ett lätt rengöringsbart material för att motverka smutsansamlingar. I lokalerna är det ofta fuktigt, därför får inte rost- eller rötbenägna material förekomma. Kylanläggningen med kylrum är den kostsammaste delen av slakteriet och det som de flesta underdimensionerar vid byggnationen. Det är viktigt att skilja på lokaler för nedkylning av kroppar och sådana lokaler som lagrar redan kylt kött. Alla djur som ska slaktas måste besiktigas tidigast 24 timmar före slakt, därefter skall slaktkropparna besiktigas inom 24 timmar efter slakt. Vanligast är att distriktsveterinären genomför besiktningarna. Enligt livsmedelslagen skall alla som producerar eller hanterar livsmedel yrkesmässigt upprätta ett egenkontrollprogram för att undvika, begränsa och eliminera de faror som kan uppstå i slakteriet när det gäller föroreningar av alla slag. HACCP är ett egenkontrollprogram där man gör en riskanalys utifrån vissa kritiska kontrollpunkter. Detta program ska alla livsmedelsföretag av industriell karaktär använda sig av. Vår erfarenhet av det här arbetet och de kontakter vi har haft med branschkunniga personer har gett oss uppfattningen att det inte är omöjligt att driva sitt eget gårdsslakteri bara tillräckligt stort intresse finns.Because of our great interest for animal welfare questions and the production of provisions with high quality we have chosen to focus on the area of yard slaughterhouse. In a time with a reduced amount of large slaughterhouses which, leads to long transportations and results in increased stress and injuries for the animals, we believe this is an important issue. We have with our report summarized what we feel is important to think about before you start your own slaughterhouse. There are different key areas you need to think of before you start. First of all you need to contact your local municipality for an approval for construction. At the same time you should also apply for an environmental permission for your activity. When this is done you should contact the national food administration with your description of activity and a drawing plan to be able to get permission to produce provisions. The national agriculture administration should be contacted to get a number for production. All activities around slaughterhouses are strictly regulated and these laws can be found at the National Food Administration or the National Agricultures websites. When you are planning and designing your building it’s important to think about the goods and personnel flow to be able to separate hygienic and unhygienic management. Animals, animal bodies and personnel shall, without crossing each others way, go from unhygienic zone to a hygienic zone. The slaughterhouse floor, walls and ceiling should be made of a material which is easy to clean and keep hygienic. These areas are often damp therefore there should be no materials which have a tendency to rust. The room containing the cold store is the expensive part of the slaughterhouse and these are often not prioritised when constructing the building. It is very important to separate the different areas for cooling of animals and areas which already store cool meat All animals which will be slaughtered have to be examined the earliest of 24 hours before the slaughter therefore all the slaughter bodies should be examined within 24 hours after the slaughter. The most common thing is for the local veterinary to carry out the examination. According to the law of provisions everyone that produces or handles provisions on a professional basis has to establish a personnel control program to avoid, limit and eliminate the dangerous pollution of all kinds which can occur in a slaughterhouse. HACCP is your own control program where you do a risk analysis on the basis of certain critical control points. This program should be used by all the provisions companies of industrial character. Our experience of this work and the contacts we have had with knowledgeable people in this area has given us an opinion that it is not impossible to run your own slaughterhouse as long as there is an interest

The amount of straw for growing-finishing pigs considering the reduction of time spent in manipulative behavior

The behavior of rooting and digging is highly motivated in the pig. The motivation to perform this exploratory behavior is not reduced even after the dietary requirement has been fulfilled through feeding. The aim of this study was to identify the minimal amounts of straw needed to satisfy pig motivation for manipulation and reduce to a minimum the manipulating behavior of pigs directed toward pen mates. To determine the minimal amount of straw needed for conventional growing-finishing pigs, a study using 168 pigs provided with 7 different amounts of straw (20, 40, 60, 80, 100, 200 or 300 grams/ pig/ day) was performed. The straw was provided either once or four times per day. Behavior observations were made using focal animal sampling and continuous recording for one hour between 9 and 10 am and between 3 and 4 pm. The time spent by the pigs manipulating straw increased over 10% ranging up to 27% in all the pens receiving over 200g of straw per day compared to the range from 4-22% in pens receiving 20-100g of straw. Meanwhile, the time spent in redirected behavior decreased below 5% in all the pens receiving over 200g of straw per day. No significant differences were found when comparing pens provided with straw once or four times per day

Long-Term Prognostic Importance of Diabetes After a Myocardial Infarction Depends on Left Ventricular Systolic Function

Objective: This study was performed to understand how left ventricular function modulates the prognostic importance of diabetes after myocardial infarction (MI). Research Design and Methods: Consecutively hospitalized MI patients screened for three clinical trials were followed for a median of 7 years. Multivariable Cox regression models were used to assess the risk of mortality associated with diabetes, and the importance of diabetes was examined independently within defined left ventricular ejection fraction (LVEF) subgroups. Results: A total of 16,912 patients were included; 1,819 (11%) had diabetes. Diabetes and 15% unit depression in LVEF were of similar prognostic importance: hazard ratios (HRs) were 1.45 (95% CI 1.37–1.54) and 1.41 (1.37–1.45) for diabetes and LVEF depression, respectively. LVEF modified the outcomes associated with diabetes, with HRs being 1.29 (1.19–1.40) and 1.61 (1.49–1.74) in patients with LVEF <40% and LVEF ≥40%, respectively (P = 0.03). Conclusions: Patients within the higher LVEF categories have a greater mortality risk attributable to diabetes than patients within the lower LVEF categories