Replication and discrimination of limb movement velocity

It is well known that proprioception is composed of the senses of movement and position. Whereas tests of position sense are quite commonly used, tests of the acuity in perception of movement velocity are scarce. In the present study we examined some novel tests for assessing the sense of limb movement velocity, involving replication and discrimination of single-joint movement velocity. Specifically, we investigated: (1) whether replication of limb movement velocity is more accurate following active criterion movements as compared to passive; (2) whether antagonist muscle contraction during passive limb movement enhances velocity discrimination; (3) how criterion movement velocity influences response accuracy; (4) the relationship between movement velocity and movement extent during velocity replication; and (5) whether subjects really base discrimination of velocities on perceived velocity. Sixteen healthy subjects participated in four tests (I-IV). For each test, horizontal abductions were performed about the right glenohumeral joint from the sagittal plane. The subjects were required to actively replicate the velocity of either an active (Test I) or passive (Test II) criterion movement, or judge whether a passive/semipassive (passive during antagonist muscle contraction) movement was faster or slower than a previous passive/semipassive criterion movement (Test III/IV). The results revealed higher response accuracy for Test I compared to Test II and for slower movements compared to faster, but no difference in response accuracy between Test III and IV. For velocity discrimination, the analysis revealed that the subjects based their judgment on the difference between criterion and comparison velocity rather than time or extent cues.     

The impact of climate on the geographical distribution of phytoplankton species in boreal lakes

Here, we use a novel space-by-time approach to study large-scale changes in phytoplankton species distribution in Swedish boreal lakes in response to climate variability. Using phytoplankton samples from 27 lakes, evenly distributed across Sweden, all relatively unimpacted by anthropogenic disturbance and sampled annually between 1996 and 2010, we found significant shifts in the geographical distribution of 18 species. We also found significant changes in the prevalence of 45 species (33 became more common and 12 less common) over the study period. Using species distribution models and phytoplankton samples from 60 lakes sampled at least twice between 1992 and 2010, we evaluated the importance of climate variability and other environmental variables on species distribution. We found that temperature (e.g., extreme events and the duration of the growing season) was the most important predictor for species detections. Many cyanobacteria, chlorophytes, and, to a lesser extent, diatoms and zygnematophytes, showed congruent and positive responses to temperature. In contrast, precipitation explained little variation and was important only for a few taxa (e.g., Staurodesmus spp., Trachelomonas volvocina). At the community level, our results suggest a change in community composition at temperatures over 20 °C and growing seasons longer than 40 days. We conclude that climate is an important driver of the distributional patterns of individual phytoplankton species and may drive changes in community composition in minimally disturbed boreal lakes.     

Derivation of Human Induced Pluripotent Stem Cells from Patients with Maturity Onset Diabetes of the Young

Maturity onset diabetes of the young (MODY) is an autosomal dominant disease. Despite extensive research, the mechanism by which a mutant MODY gene results in monogenic diabetes is not yet clear due to the inaccessibility of patient samples. Induced pluripotency and directed differentiation toward the pancreatic lineage are now viable and attractive methods to uncover the molecular mechanisms underlying MODY. Here we report, for the first time, the derivation of human induced pluripotent stem cells (hiPSCs) from patients with five types of MODY: MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), MODY5 (HNF1B), and MODY8 (CEL) with a polycistronic lentiviral vector expressing a Cre-excisable human “stem cell cassette” containing the four reprogramming factors OCT4, KLF4, SOX2, and CMYC. These MODY-hiPSCs morphologically resemble human pluripotent stem cells (hPSCs), express pluripotency markers OCT4, SOX2, NANOG, SSEA-4, and TRA-1–60, give rise to derivatives of the three germ layers in a teratoma assay, and are karyotypically normal. Overall, our MODY-hiPSCs serve as invaluable tools to dissect the role of MODY genes in the development of pancreas and islet cells and to evaluate their significance in regulating beta cell function. This knowledge will aid future attempts aimed at deriving functional mature beta cells from hPSCs.     

Regulatory T Cells Prevent Th2 Immune Responses and Pulmonary Eosinophilia during Respiratory Syncytial Virus Infection in Mice

During viral infection, inflammation and recovery are tightly controlled by competing proinflammatory and regulatory immune pathways. Respiratory syncytial virus (RSV) is the leading global cause of infantile bronchiolitis, which is associated with recurrent wheeze and asthma diagnosis in later life. Th2-driven disease has been well described under some conditions for RSV-infected mice. In the present studies, we used the Foxp3^DTR mice (which allow specific conditional depletion of Foxp3⁺ T cells) to investigate the functional effects of regulatory T cells (Tregs) during A2-strain RSV infection. Infected Treg-depleted mice lost significantly more weight than wild-type mice, indicating enhanced disease. This enhancement was characterized by increased cellularity in the bronchoalveolar lavage (BAL) fluid and notable lung eosinophilia not seen in control mice. This was accompanied by abundant CD4⁺ and CD8⁺ T cells exhibiting an activated phenotype and induction of interleukin 13 (IL-13)- and GATA3-expressing Th2-type CD4⁺ T cells that remained present in the airways even 14 days after infection. Therefore, Treg cells perform vital anti-inflammatory functions during RSV infection, suppressing pathogenic T cell responses and inhibiting lung eosinophilia. These findings provide additional evidence that dysregulation of normal immune responses to viral infection may contribute to severe RSV disease.     

The impact of nandrolone decanoate and growth hormone on biosynthesis of steroids in rats

Growth hormone (GH) and anabolic androgenic steroids (AAS) are commonly used in sports communities. Several studies have suggested an association between GH and AAS. We have investigated the impact of GH in rats treated with nandrolone decanoate (ND). Male Wistar rats received ND (15 mg/kg) every third day during three weeks and were subsequently treated with recombinant human GH (1.0 IU/kg) for ten consecutive days. Plasma samples were collected and peripheral organs (i.e. heart, liver, testis and thymus) were dissected and weighed. Concentration of thirteen endogenous steroids was measured in the rat plasma samples using high specificity LC–MS/MS methods. Seven steroids were detected and quantified, and concentrations of estrone, testosterone, and androstenedione were significantly different among the groups, while concentrations of pregnenolone, DHEA, 17-hydroxyprogesterone and corticosterone were not altered. Administration of rhGH alone altered the plasma steroid distribution, and the results demonstrated significantly increased concentrations of plasma estrone as well as decreased concentrations of testosterone and androstenedione in the ND-treated rats. Administration of rhGH to ND-pretreated rats did not reverse the alteration of the steroid distribution induced by ND. Administration of ND decreased the weight of the thymus, and addition of rhGH did not reverse this reduction. However, rhGH administration induced an enlargement of thymus. Taken together, the plasma steroid profile differed in the four groups, i.e. control, AAS, rhGH and the combination of AAS and rhGH treatment.     

Patterns in Size,Sex Ratio and Time at Emergence in a South Swedish Population of Sympetrum sanguineum (Odonata)

Differences between sexes in life history patterns of Sympetrum sanguineum were studied in a small pond in southern Sweden by means of exuviae and adult sampling. Emergence occurred from 4 to 28 July, and mean emergence date was 10 July for both males and females. The sex ratio at emergence (53% females) did not differ from 1:1, but significantly more females emerged during the first 5 days of the emergence period. Size of emerging individuals (immatures) decreased as season progressed and males emerged at a larger size than females. While immature males were heavier than immature females, no such difference was found in mature individuals. We suggest that the sexual differences in size and emergence patterns observed are the result of different optimisation by males and females with respect to the growth-mortality risk trade-off in the larval and adult stages.     

SHORT Syndrome with Partial Lipodystrophy Due to Impaired Phosphatidylinositol 3 Kinase Signaling

The phosphatidylinositol 3 kinase (PI3K) pathway regulates fundamental cellular processes such as metabolism, proliferation, and survival. A central component in this pathway is the p85α regulatory subunit, encoded by PIK3R1. Using whole-exome sequencing, we identified a heterozygous PIK3R1 mutation (c.1945C>T [p.Arg649Trp]) in two unrelated families affected by partial lipodystrophy, low body mass index, short stature, progeroid face, and Rieger anomaly (SHORT syndrome). This mutation led to impaired interaction between p85α and IRS-1 and reduced AKT-mediated insulin signaling in fibroblasts from affected subjects and in reconstituted Pik3r1-knockout preadipocytes. Normal PI3K activity is critical for adipose differentiation and insulin signaling; the mutated PIK3R1 therefore provides a unique link among lipodystrophy, growth, and insulin signaling.     

The role of observers' gaze behaviour when watching object manipulation tasks: predicting and evaluating the consequences of action

When watching an actor manipulate objects, observers, like the actor, naturally direct their gaze to each object as the hand approaches and typically maintain gaze on the object until the hand departs. Here, we probed the function of observers'' eye movements, focusing on two possibilities: (i) that observers'' gaze behaviour arises from processes involved in the prediction of the target object of the actor''s reaching movement and (ii) that this gaze behaviour supports the evaluation of mechanical events that arise from interactions between the actor''s hand and objects. Observers watched an actor reach for and lift one of two presented objects. The observers'' task was either to predict the target object or judge its weight. Proactive gaze behaviour, similar to that seen in self-guided action–observation, was seen in the weight judgement task, which requires evaluating mechanical events associated with lifting, but not in the target prediction task. We submit that an important function of gaze behaviour in self-guided action observation is the evaluation of mechanical events associated with interactions between the hand and object. By comparing predicted and actual mechanical events, observers, like actors, can gain knowledge about the world, including information about objects they may subsequently act upon.