The effect of insulin on milk production

Det är mjölkkörtlarna som från näringsämnen i blodet bygger upp mjölkens fett, laktos och det mesta av proteinet. Mjölkutsöndringen regleras bland annat av hormonella koncentrationer i blodet, lokala förhållanden i alveolen, näringsämnen i blodet samt blodflödet till juvret. Hormonet insulin är den viktigaste anabola signalmolekylen i kroppen men nötkreaturs juver är inte beroende av insulin för upptag av glukos. Trots det är insulin ett viktigt hormon när det gäller syntesen av mjölk och mjölkens komponenter. Syftet med denna litteraturstudie var att ta reda på hur insulin påverkar mjölkproduktionen hos nötkreatur med fokus på mjölkavkastning samt mängd mjölkfett och mjölkprotein. Effekten av insulin påverkas av laktationsstadie och energibalans. Experimentell insulinbehandling i tidig laktation kan eventuellt minska mjölkavkastningen medan den inte påverkas när kon är i mitten av laktationen. Överlag kan en ökning ses i mängden mjölkprotein vid experimentell insulinbehandling, men ökningen begränsas av aminosyratillgången. Mjölkfettsinnehållet förblir oförändrat i de flesta fall av experimentell insulinbehandling, men en minskning kan ske och det främst då kon är i negativ energibalans.It is the mammary glands that synthesise milk fat, lactose and most of the protein found in milk from nutrients in the blood. Milk secretion is regulated by hormonal blood levels, local conditions in the alveoli, blood flow and nutrient content in blood. The hormone insulin is the most important anabolic signal molecule in the body, but the bovine udder does not depend on insulin for glucose uptake. However, insulin has other effects on synthesis of milk and milk components. The purpose of this study was to investigate how insulin affects milk production in cattle with respect to milk yield and the amount of milk fat and milk protein. The effects of insulin depend on stage of lactation and energy balance. In mid lactation milk yield is not affected by changes in plasma insulin, but yield may be reduced when insulin is high during early lactation. Overall, an increase in insulin is shown in the amount of milk protein when insulin is increased experimentally. The increase is limited by the amino acid availability. Milk fat content remains unchanged in most cases of experimental insulin treatment, but there are also reports of reduced milk fat content when insulin is elevated. This milk fat reduction happens mainly when the cows are in the presences of a negative energy balance

Cow traffic in an automatic milking rotary system

Automatic milking systems and automatic milking rotary systems (AMR) where the cows are gathered and held in a waiting area prior to milking are dependent on cows to enter the milking unit voluntarily. A low rate of cows that voluntarily enter the milking unit affects both the economy, working safety and cow health negatively. Both the flow of animals as well as the interactions in this enclosed area can be affected by various designs of the waiting area. The present study examined dairy cow behaviour, milking time and labour in an AMR with two different waiting area designs: with parallel guiding or no parallel guiding. The parallel guiding consisted of two railings placed in front of the entrance to the AMR. These railings separated the cows, creating what could be seen as three corridors in front of the AMR. A control treatment without parallel guiding and a treatment with parallel guiding was applied for two weeks each. Two groups, G1 and G2, of approximately 60 lactating cows each of Swedish Red and Swedish Holstein breeds were included in the study. The G1 group consisted of mainly primiparous cows and G2 of mainly multiparous cows. For analysis of the behaviours, 20 focal animals were marked in each group. The staff gathered the cows in one of the two waiting area designs prior to milking but were not permitted to interact with the cows for 40 minutes after that. During these 40 minutes, the cow behaviour was studied. An ethogram was used. For example, it was noted if a cow pushed another cow. Both the performing and the receiving animal was noted. When 40 minutes had passed, the staff were allowed to fetch cows that had not entered the AMR. The period from the staff’s first interaction to the last cow entering the milking unit was also studied, each time staff interacted with a cow was noted as well at the total time for staff interaction. Data was collected during 6 milking occasions per group on the second week of each treatment. This was performed twice for each treatment, resulting in a total of 48 milking occasions studied, 24 during each treatment. The results showed a lower frequency of behaviours when parallel guiding was practised (p=0.04), as well as lower total staff interaction time (p=0.04) and staff interactions (p=0.0002). The majority of behaviours were performed by the lightest (40%) or heaviest animals (37%), and multiparous cows (58%). The number of performed, as well as received behaviours, seemed to be increasing with days in milk. The animal receiving a behaviour was in most cases primiparous cows (63%). The majority of the staff interactions were also performed on first parity cows (57%) and the heaviest cows (50%). The number of received staff interactions seemed to be increasing with days in milk. No difference was found between treatments in total time for milking, total walking and waiting time before milking or time spent in waiting area. Neither was a difference found regarding the time spent in waiting area as a group retrieved from the video recordings. However, the parallel guiding did overall not result in longer time intervals when compared to no parallel guiding. The milk yield during the periods when parallel guiding was practised was found to be higher compared to when no parallel guiding was practised (p<.0001). The parallel guiding was not found to have any negative effects on either working time, animal behaviour or milk yield. Further studies are needed to investigate the effects of the parallel guiding in more depth

The immersion freezing behavior of ash particles from wood and brown coal burning

It is generally known that ash particles from coal combustion can trigger ice nucleation when they interact with water vapor and/or supercooled droplets. However, data on the ice nucleation of ash particles from different sources, including both anthropogenic and natural combustion processes, are still scarce. As fossil energy sources still fuel the largest proportion of electric power production worldwide, and biomass burning contributes significantly to the global aerosol loading, further data are needed to better assess the ice nucleating efficiency of ash particles. In the framework of this study, we found that ash particles from brown coal (i.e., lignite) burning are up to 2 orders of magnitude more ice active in the immersion mode below −32 °C than those from wood burning. Fly ash from a coal-fired power plant was shown to be the most efficient at nucleating ice. Furthermore, the influence of various particle generation methods on the freezing behavior was studied. For instance, particles were generated either by dispersion of dry sample material, or by atomization of ash–water suspensions, and then led into the Leipzig Aerosol Cloud Interaction Simulator (LACIS) where the immersion freezing behavior was examined. Whereas the immersion freezing behavior of ashes from wood burning was not affected by the particle generation method, it depended on the type of particle generation for ash from brown coal. It was also found that the common practice of treating prepared suspensions in an ultrasonic bath to avoid aggregation of particles led to an enhanced ice nucleation activity. The findings of this study suggest (a) that ash from brown coal burning may influence immersion freezing in clouds close to the source and (b) that the freezing behavior of ash particles may be altered by a change in sample preparation and/or particle generation

The gut microbiota and developmental programming of the testis in mice

Nutrients and environmental chemicals, including endocrine disruptors, have been incriminated in the current increase in male reproductive dysfunction, but the underlying mechanisms remain unknown. The gastrointestinal tract represents the largest surface area exposed to our environment and thereby plays a key role in connection with exposure of internal organs to exogenous factors. In this context the gut microbiome (all bacteria and their metabolites) have been shown to be important contributors to body physiology including metabolism, cognitive functions and immunity. Pivotal to male reproduction is a proper development of the testis, including the formation of the blood-testis barrier (BTB) that encapsulates and protects germ cells from stress induced environmental cues, e.g. pathogenic organisms and xenobiotics. Here we used specific pathogen free (SPF) mice and germ-free (GF) mice to explore whether gut microbiota and/or their metabolites can influence testis development and regulation of BTB. Lumen formation in the seminiferous tubules, which coincides with the development of the BTB was delayed in the testes of GF mice at 16 days postpartum. In addition, perfusion experiments (Evans blue) demonstrated increased BTB permeability in these same mice. Reduced expressions of occludin, ZO-2 and E-cadherin in GF testis suggested that the microbiota modulated BTB permeability by regulation of cell-cell adhesion. Interestingly, exposure of GF mice to Clostridium Tyrobutyricum (CBUT), which secrete high levels of butyrate, restored the integrity of the BTB and normalized the levels of cell adhesion proteins. Moreover, the GF mice exhibited lower serum levels of gonadotropins (LH and FSH) than the SPF group. In addition, the intratesticular content of testosterone was lower in GF compared to SPF or CBUT animals. Thus, the gut microbiome can modulate the permeability of the BTB and might play a role in the regulation of endocrine functions of the testis.Scopu

Outbreak of Puumala Virus Infection, Sweden

An unexpected and large outbreak of Puumala virus infection in Sweden resulted in 313 nephropathia epidemica patients/100,000 persons in Västerbotten County during 2007. An increase in the rodent population, milder weather, and less snow cover probably contributed to the outbreak

Defining the genetic susceptibility to cervical neoplasia - a genome-wide association study

Funding: MAB was funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. Support was also received from the Australian Cancer Research Foundation. JL holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. The Seattle study was supported by the following grants: NIH, National Cancer Institute grants P01CA042792 and R01CA112512. Cervical Health Study (from which the NSW component was obtained) was funded by NHMRC Grant 387701, and CCNSW core grant. The Montreal study was funded by the Canadian Institutes of Health Research (grant MOP-42532) and sample processing was funded by the Reseau FRQS SIDA-MI. The Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg and Umeå, the Lundberg Foundation, the Torsten and Ragnar Soderberg’s Foundation, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS, BBMRI.se, the Swedish Society of Medicine, the KempeFoundation (JCK-1021), the Medical Faculty of Umeå University, the County Council of Vasterbotten (Spjutspetsanslag VLL:159:33-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PDFPublisher PD

Nebulin nemaline myopathy recapitulated in a compound heterozygous mouse model with both a missense and a nonsense mutation in Neb

Nemaline myopathy (NM) caused by mutations in the gene encoding nebulin (NEB) accounts for at least 50% of all NM cases worldwide, representing a significant disease burden. Most NEB-NM patients have autosomal recessive disease due to a compound heterozygous genotype. Of the few murine models developed for NEB-NM, most are Neb knockout models rather than harbouring Neb mutations. Additionally, some models have a very severe phenotype that limits their application for evaluating disease progression and potential therapies. No existing murine models possess compound heterozygous Neb mutations that reflect the genotype and resulting phenotype present in most patients. We aimed to develop a murine model that more closely matched the underlying genetics of NEB-NM, which could assist elucidation of the pathogenetic mechanisms underlying the disease. Here, we have characterised a mouse strain with compound heterozygous Neb mutations; one missense (p.Tyr2303His), affecting a conserved actin-binding site and one nonsense mutation (p.Tyr935*), introducing a premature stop codon early in the protein. Our studies reveal that this compound heterozygous model, Neb(Y2303H, Y935X), has striking skeletal muscle pathology including nemaline bodies. In vitro whole muscle and single myofibre physiology studies also demonstrate functional perturbations. However, no reduction in lifespan was noted. Therefore, Neb(Y2303H,Y935X) mice recapitulate human NEB-NM and are a much needed addition to the NEB-NM mouse model collection. The moderate phenotype also makes this an appropriate model for studying NEB-NM pathogenesis, and could potentially be suitable for testing therapeutic applications.Peer reviewe

Nebulin nemaline myopathy recapitulated in a compound heterozygous mouse model with both a missense and a nonsense mutation in Neb

Nemaline myopathy (NM) caused by mutations in the gene encoding nebulin (NEB) accounts for at least 50% of all NM cases worldwide, representing a significant disease burden. Most NEB-NM patients have autosomal recessive disease due to a compound heterozygous genotype. Of the few murine models developed for NEB-NM, most are Neb knockout models rather than harbouring Neb mutations. Additionally, some models have a very severe phenotype that limits their application for evaluating disease progression and potential therapies. No existing murine models possess compound heterozygous Neb mutations that reflect the genotype and resulting phenotype present in most patients. We aimed to develop a murine model that more closely matched the underlying genetics of NEB-NM, which could assist elucidation of the pathogenetic mechanisms underlying the disease. Here, we have characterised a mouse strain with compound heterozygous Neb mutations; one missense (p.Tyr2303His), affecting a conserved actin-binding site and one nonsense mutation (p.Tyr935*), introducing a premature stop codon early in the protein. Our studies reveal that this compound heterozygous model, Neb(Y2303H, Y935X), has striking skeletal muscle pathology including nemaline bodies. In vitro whole muscle and single myofibre physiology studies also demonstrate functional perturbations. However, no reduction in lifespan was noted. Therefore, Neb(Y2303H,Y935X) mice recapitulate human NEB-NM and are a much needed addition to the NEB-NM mouse model collection. The moderate phenotype also makes this an appropriate model for studying NEB-NM pathogenesis, and could potentially be suitable for testing therapeutic applications.Peer reviewe

Actin Nemaline Myopathy Mouse Reproduces Disease, Suggests Other Actin Disease Phenotypes and Provides Cautionary Note on Muscle Transgene Expression

Mutations in the skeletal muscle α-actin gene (ACTA1) cause congenital myopathies including nemaline myopathy, actin aggregate myopathy and rod-core disease. The majority of patients with ACTA1 mutations have severe hypotonia and do not survive beyond the age of one. A transgenic mouse model was generated expressing an autosomal dominant mutant (D286G) of ACTA1 (identified in a severe nemaline myopathy patient) fused with EGFP. Nemaline bodies were observed in multiple skeletal muscles, with serial sections showing these correlated to aggregates of the mutant skeletal muscle α-actin-EGFP. Isolated extensor digitorum longus and soleus muscles were significantly weaker than wild-type (WT) muscle at 4 weeks of age, coinciding with the peak in structural lesions. These 4 week-old mice were ∼30% less active on voluntary running wheels than WT mice. The α-actin-EGFP protein clearly demonstrated that the transgene was expressed equally in all myosin heavy chain (MHC) fibre types during the early postnatal period, but subsequently became largely confined to MHCIIB fibres. Ringbinden fibres, internal nuclei and myofibrillar myopathy pathologies, not typical features in nemaline myopathy or patients with ACTA1 mutations, were frequently observed. Ringbinden were found in fast fibre predominant muscles of adult mice and were exclusively MHCIIB-positive fibres. Thus, this mouse model presents a reliable model for the investigation of the pathobiology of nemaline body formation and muscle weakness and for evaluation of potential therapeutic interventions. The occurrence of core-like regions, internal nuclei and ringbinden will allow analysis of the mechanisms underlying these lesions. The occurrence of ringbinden and features of myofibrillar myopathy in this mouse model of ACTA1 disease suggests that patients with these pathologies and no genetic explanation should be screened for ACTA1 mutations

AhR controls redox homeostasis and shapes the tumor microenvironment in BRCA1-associated breast cancer

Cancer cells have higher reactive oxygen species (ROS) than normal cells, due to genetic and metabolic alterations. An emerging scenario is that cancer cells increase ROS to activate protumorigenic signaling while activating antioxidant pathways to maintain redox homeostasis. Here we show that, in basal-like and BRCA1-related breast cancer (BC), ROS levels correlate with the expression and activity of the transcription factor aryl hydrocarbon receptor (AhR). Mechanistically, ROS triggers AhR nuclear accumulation and activation to promote the transcription of both antioxidant enzymes and the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG). In a mouse model of BRCA1-related BC, cancer-associated AhR and AREG control tumor growth and production of chemokines to attract monocytes and activate proangiogenic function of macrophages in the tumor microenvironment. Interestingly, the expression of these chemokines as well as infiltration of monocyte-lineage cells (monocyte and macrophages) positively correlated with ROS levels in basal-like BC. These data support the existence of a coordinated link between cancer-intrinsic ROS regulation and the features of tumor microenvironment. Therapeutically, chemical inhibition of AhR activity sensitizes human BC models to Erlotinib, a selective EGFR tyrosine kinase inhibitor, suggesting a promising combinatorial anticancer effect of AhR and EGFR pathway inhibition. Thus, AhR represents an attractive target to inhibit redox homeostasis and modulate the tumor promoting microenvironment of basal-like and BRCA1-associated BC