Effects of extruded or pelleted diet on blood glucose, body weight, feed and water consumption in rats

Extruded diets are claimed to be more digestible, palatable and of a higher hygienic standard compared to pelleted diets. In a comparision of a pelleted and an extruded diet given to Sprague-Dawley rats, we found no difference in weight gain, feed and water consumption or in blood glucose level. In the microbiological analyses, there was no major difference either. When considering choice of diet the physical form seems to be of minor importance. The major factors should be the nutritional value, hygienic level (autoclavable or irradiated vs conventional), reproduciability, availability, confidence in producer and economical values

Are female mice dehydrated during peak lactation? Effect of water and gel supplement on hydration parameters and water consumption in two strains of mice

Mice (Mus musculus) have a high basal rate of metabolism which increases during pregnancy and lactation. During peak lactation, water intake amounts to up to 65 % of the bodyweight per day. Providing water in a bottle may pose a restriction of water intake and lead to dehydration during periods of high demand, such as peak lactation. To establish if female mice are able to sustain a physiological hydration status during peak lactation, a completely randomized factorial design study was conducted with 12 RjOrl:SWISS (SWISS) and 12 C57BL/6JRj (B6) six-week old female mice in breeding. Female mice were randomly assigned to one of three groups with different watering alternatives: water bottle (Standard, n=6); water bottle + sachet with 98 % water gel (Gel, n=6); or water bottle + water bowl (Bowl, n=6). Non-mated females, provided with water bottles, served as controls (n=6). Hydration parameters [total protein (TP), hemoglobin, hematocrit, serum osmolality (Osmol), blood urea nitrogen (BUN)] and magnesium were measured in blood before mating (Pre) and during peak lactation (Peak), and at the same time points in controls. Water bottles were weighed during lactation and body weights of females and litters recorded at weaning. Data were analyzed by parametric or non-parametric methods to evaluate effects of strain, group and time point. The hydration parameters and magnesium were mostly within normal ranges in all animals at Pre and Peak. TP was lower at Peak in all lactating groups compared to Controls and to Pre (p<0.01). Mice in group Bowl consumed 54 % less bottle water compared with Gel and Standard (p<0.001), had 34 % lower levels of BUN than Standard and Control (p<0.01) and 5 % lower serum osmolality at Peak than Pre (p<0.01).Conclusion: Female mice are not dehydrated at peak lactation. However, they prefer to drink, and seemingly drink more water, from a bowl than from a bottle

I jakt på en metod - från lineärt till icke-lineärt skrivande

From linear to non-linear writing, this paper is an attempt to map out the writing process by looking at the way that a number of published authors work as they compose their stories. It is also a look into the development of my own writing process as I have moved from writing linearly – from beginning to end – to a non-linear fashion – of writing scenes out of order – during my three years at Författarskolan, Lunds University. This paper not only tries to depict the hows, but also the whys, trying to close in on the reason why a specific writer works in his or her chosen fashion

Factors associated with endowed chair allocation in medical oncology in the United States

To explore persisting gender disparities across leadership roles in medicine, we examined factors associated with holding endowed chairs in US oncology divisions. In 2019, we identified 95 academic oncology divisions, using the Oncology Division Chiefs and Department Chairs listing in the American Society of Clinical Oncology myConnection forum. We collected public information on gender, degree, total National Institutes of Health funding as principal investigator, H-indices, publication and citation numbers, and graduation year and constructed a multivariable logistic regression model. All statistical tests were 2-sided. We identified 1087 oncology full professors. Of these, 287 (26.4%) held endowed chairs: 60 of 269 women (22.3%) vs 227 of 818 men (27.8%) (P = .08). On multivariable analysis, greater research productivity and National Institutes of Health funding were associated with having an endowed chair (P \u3c .001), whereas gender was not (P = .45). Though sample size was limited, if gender differences are in fact smaller in certain subspecialties than other fields of internal medicine, insights might emerge to guide efforts to promote equity

Implementation of a Shared Data Repository and Common Data Dictionary for Fetal Alcohol Spectrum Disorders Research

Many previous attempts by fetal alcohol spectrum disorders researchers to compare data across multiple prospective and retrospective human studies have failed due to both structural differences in the collected data as well as difficulty in coming to agreement on the precise meaning of the terminology used to describe the collected data. Although some groups of researchers have an established track record of successfully integrating data, attempts to integrate data more broadly amongst different groups of researchers have generally faltered. Lack of tools to help researchers share and integrate data has also hampered data analysis. This situation has delayed improving diagnosis, intervention, and treatment before and after birth. We worked with various researchers and research programs in the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CI-FASD) to develop a set of common data dictionaries to describe the data to be collected, including definitions of terms and specification of allowable values. The resulting data dictionaries were the basis for creating a central data repository (CI-FASD Central Repository) and software tools to input and query data. Data entry restrictions ensure that only data which conform to the data dictionaries reach the CI-FASD Central Repository. The result is an effective system for centralized and unified management of the data collected and analyzed by the initiative, including a secure, long-term data repository. CI-FASD researchers are able to integrate and analyze data of different types, collected using multiple methods, and collected from multiple populations, and data are retained for future reuse in a secure, robust repository

Identification of a Novel “Almost Neutral” Mu Opioid Receptor Antagonist in CHO Cells Expressing the Cloned Human Mu Opioid Receptor

The basal (constitutive) activity of G protein-coupled receptors allows for the measurement of inverse agonist activity. Some competitive antagonists turn into inverse agonists under conditions where receptors are constitutively active. In contrast, neutral antagonists have no inverse agonist activity, and they block both agonist and inverse agonist activity. The mu opioid receptor (MOR) demonstrates detectable constitutive activity only after a state of dependence is produced by chronic treatment with a MOR agonist. We therefore sought to identify novel MOR inverse agonists, and novel neutral MOR antagonists in both untreated and agonist-treated MOR cells. CHO cells expressing the cloned human mu receptor (hMOR-CHO cells) were incubated for 20 hr with medium (control) or 10 μM (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(benzoyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester (herkinorin, HERK). HERK-treatment generates a high degree of basal signaling and enhances the ability to detect inverse agonists. [35S]-GTP-γ-S assays were conducted using established methods. We screened 21 MOR “antagonists” using membranes prepared from HERK-treated hMOR-CHO cells. All antagonists, including CTAP and 6β-naltrexol, were inverse agonists. However, LTC-2 7 4 ( (-)-3-cyclopropylmethyl-2,3,4,4aα,5,6,7,7aα-octahydro-1H-benzofuro[3,2-e]isoquinolin-9-ol)) showed the lowest efficacy as an inverse agonist, and, at concentrations less than 5 nM, had minimal effects on basal [35S]-GTP-γ-S binding. Other efforts in this study identified KC-2-009 ((+)-3-((1R,5S)-2-((Z)-3-Phenylallyl)-2-azabicyclo[3.3.1]nonan-5-yl)phenol hydrochloride) as an inverse agonist at untreated MOR cells. In HERK-treated cells, KC-2-009 had the highest efficacy as an inverse agonist. In summary, we identified a novel and selective MOR inverse agonist (KC-2-009), and a novel MOR antagonist (LTC-274) that shows the least inverse agonist activity among 21 MOR antagonists. LTC-274 is a promising lead compound for developing a true MOR neutral antagonist

Implementation of a Distributed Architecture for Managing Collection and Dissemination of Data for Fetal Alcohol Spectrum Disorder

We implemented a distributed system for management of data for an international collaboration studying Fetal Alcohol Spectrum Disorders (FASD). Subject privacy was protected, researchers without dependable Internet access were accommodated, and researchers’ data were shared globally. Data dictionaries codified the nature of the data being integrated, data compliance was assured through multiple consistency checks, and recovery systems provided a secure, robust, persistent repository. The system enabled new types of science to be done, using distributed technologies that are expedient for current needs while taking useful steps towards integrating the system in a future grid-based cyberinfrastructure. The distributed architecture, verification steps, and data dictionaries suggest general strategies for researchers involved in collaborative studies, particularly where data must be de-identified before being shared. The system met both the collaboration’s needs and the NIH Roadmap’s goal of wide access to databases that are robust and adaptable to researchers’ needs

Tillstånd och trender för arter och deras livsmiljöer

2015 års upplaga av den svenska rödlistan är den fjärde i ordningen. Den är baserad på IUCN:s rödlistningskriterier och revideras vart femte år. I rödlistan bedöms risken som enskilda arter av djur, växter och svampar löper att försvinna från Sverige. Bedömningen utförs av ArtDatabankens medarbetare i samverkan med över 100 externa experter, indelade i 14 expertkommittéer för olika organismgrupper. Under arbetet med 2015 års rödlista har tillstånd och trender bedömts för 21 600 arter och 1 318 lägre taxa (apomiktiska arter, underarter och varieteter), sammanlagt ca 22 900 taxa. Av de bedömda arterna klassificerades 2 029 som hotade (kategorierna CR, EN och VU) och 4 273 som rödlistade (inkluderar även kategorierna NT, RE och DD). Förhållandet mellan antalet rödlistade och antalet bedömda arter ar 19,8 %, vilket är ungefär samma värde som 2010 och 2005. I denna rapport jämförs antalet och andelen rödlistade arter mellan olika organismgrupper, biotoper, substrat och påverkansfaktorer. Texten ar indelad i en allmän del och åtta kapitel inriktade på olika landskapstyper. Landskapstyperna utgör en grov indelning av landets miljöer enligt följande kategorier: Skog, Jordbrukslandskap, Urbana miljöer, Fjäll, Våtmarker, Sötvatten, Havsstränder och Havsmiljöer. Skogen och jordbrukslandskapet är de artrikaste landskapstyperna med 1 800 respektive 1 400 arter som har en stark anknytning dit, och ytterligare flera hundra arter som förekommer där mer sporadiskt. De faktorer som påverkar flest rödlistade arter i Sverige är skogsavverkning och igenväxning, som båda utgör ett hot mot vardera ca 30 % av de rödlistade arterna. Avverkning minskar arealen av skog där naturliga strukturer och naturlig dynamik upprätthålls, och den orsakar därmed förlust av livsmiljöer. Igenväxning orsakas av ett antal faktorer, bland annat upphörande hävd (bete och slåtter), gödsling, trädplantering och brist på naturliga störningsregimer som t.ex. regelbundna översvämningar kring vattendrag och sjöar. Andra viktiga påverkansfaktorer är fiske, torrläggning av våtmarker, tillbakagång hos värdarter (främst alm och ask som drabbats av invasiva svampsjukdomar), klimatförändringar och konkurrens från invasiva arter. IUCN:s rödlisteindex beräknas för ett urval av de bedömda organismgrupperna. Rödlisteindex visar att skillnaderna mellan rödlistorna från 2000, 2005, 2010 och 2015 är små. Ett par undantag finns dock. Groddjur och stora däggdjur har fått en något förbättrad situation sedan 2000. Totalt förefaller det ändå som att trycket mot Sveriges artstock har förblivit relativt konstant under de senaste 15 åren

PAM-flexible genome editing with an engineered chimeric Cas9

CRISPR enzymes require a defined protospacer adjacent motif (PAM) flanking a guide RNA-programmed target site, limiting their sequence accessibility for robust genome editing applications. In this study, we recombine the PAM-interacting domain of SpRY, a broad-targeting Cas9 possessing an NRN > NYN (R = A or G, Y = C or T) PAM preference, with the N-terminus of Sc + +, a Cas9 with simultaneously broad, efficient, and accurate NNG editing capabilities, to generate a chimeric enzyme with highly flexible PAM preference: SpRYc. We demonstrate that SpRYc leverages properties of both enzymes to specifically edit diverse PAMs and disease-related loci for potential therapeutic applications. In total, the approaches to generate SpRYc, coupled with its robust flexibility, highlight the power of integrative protein design for Cas9 engineering and motivate downstream editing applications that require precise genomic positioning