Coexistence of three microsporidia parasites in populations of the freshwater amphipod Gammarus roeseli: evidence for vertical transmission and positive effect on reproduction

We investigated the prevalence, transmission mode and fitness effects of infections by obligatory intracellular, microsporidian parasites in the freshwater amphipod Gammarus roeseli. We found three different microsporidia species in this host, all using transovarial (vertical) transmission. All three coexist at different prevalences in two host populations, but bi-infected individuals were rarely found, suggesting no (or very little) horizontal transmission. It is predicted that vertically-transmitted parasites may exhibit sex-specific virulence in their hosts, or they may have either positive or neutral effects on host fitness. All three species differed in their transmission efficiency and infection intensity and our data suggest that these microsporidia exert sex-specific virulence by feminising male hosts. The patterns of infection we found exhibit convergent evolution with those of another amphipod host, Gammarus duebeni. Interestingly, we found that infected females breed earlier in the reproductive season than uninfected females. This is the first study, to our knowledge, to report a positive effect of microsporidian infection on female host reproduction.     

Sarcoglycan Complex: IMPLICATIONS FOR METABOLIC DEFECTS IN MUSCULAR DYSTROPHIES*

The sarcoglycans are known as an integral subcomplex of the dystrophin glycoprotein complex, the function of which is best characterized in skeletal muscle in relation to muscular dystrophies. Here we demonstrate that the white adipocytes, which share a common precursor with the myocytes, express a cell-specific sarcoglycan complex containing β-, δ-, and ϵ-sarcoglycan. In addition, the adipose sarcoglycan complex associates with sarcospan and laminin binding dystroglycan. Using multiple sarcoglycan null mouse models, we show that loss of α-sarcoglycan has no consequence on the expression of the adipocyte sarcoglycan complex. However, loss of β- or δ-sarcoglycan leads to a concomitant loss of the sarcoglycan complex as well as sarcospan and a dramatic reduction in dystroglycan in adipocytes. We further demonstrate that β-sarcoglycan null mice, which lack the sarcoglycan complex in adipose tissue and skeletal muscle, are glucose-intolerant and exhibit whole body insulin resistance specifically due to impaired insulin-stimulated glucose uptake in skeletal muscles. Thus, our data demonstrate a novel function of the sarcoglycan complex in whole body glucose homeostasis and skeletal muscle metabolism, suggesting that the impairment of the skeletal muscle metabolism influences the pathogenesis of muscular dystrophy.Muscle fat infiltration is recognized as a hallmark pathological feature in dystrophin glycoprotein complex (DGC)³-related muscular dystrophies (1) that include dystrophinopathies (2, 3) and sarcoglycanopathies (LGMD2C-F) (4). In agreement, magnetic resonance imaging measurements of fat infiltration allow accurate assessments of disease severity in Duchenne muscular dystrophy patients (3). Association of adipose tissue development with degenerative/regenerative or atrophic changes in skeletal muscle is also supported by the finding that adipogenesis-competent cells within the skeletal muscle are activated during muscle regeneration (5). However, the molecular mechanism(s) underlying muscle fatty metamorphosis remain unclear.Ectopic fat deposition in skeletal muscles is primarily described in animals and humans with lipodystrophy and sarcopenia. In these conditions, the accumulation of lipids and adipocytes in skeletal muscle is often accompanied by hyperglycemia and insulin resistance (6–11), both of which are strong indicators of muscle metabolic defects (12, 13) and deregulated adipogenesis (14). Furthermore, both adipose-derived and muscle-derived stem cells differentiate into adipocytes upon exposure to high levels of glucose (15), linking impaired muscle metabolism with muscle fat deposition.It is long held that the biogenesis of a basement membrane takes place in the earliest steps of adipogenesis and that extensive extracellular matrix (ECM) remodeling occurs throughout adipogenesis (16, 17). The concept that cell surface receptors play a role in the regulation of adipogenesis and thus may underlie metabolic disorders just recently emerged with a study of the integrin complexes (18). Given that the DGC in its capacity as an ECM receptor is critical for muscle integrity (19, 20) and that white adipocytes and skeletal muscle cells originate from the same mesenchymal precursor cells (21, 22), we set out to determine whether components of the skeletal muscle DGC are expressed in white adipocytes. Herein, we describe a unique adipose sarcoglycan (SG) complex that includes β-, δ-, and ϵ-SG. This complex is tightly associated with sarcospan (Sspn) and dystroglycan (DG). Moreover, we show that DG functions as a novel ECM receptor in white adipocytes. Because adipose tissue and skeletal muscle play critical roles in the maintenance of normal glucose homeostasis and whole body insulin sensitivity (23), we examined the metabolic consequences of the SG complex disruption in both adipose tissue and skeletal muscle. Using in vivo approaches, we observed that the β-SG null mouse (24), a mouse model of muscular dystrophy, is glucose-intolerant and exhibits whole body insulin resistance specifically due to impaired insulin-stimulated glucose uptake in skeletal muscle.     

One falls,we all fall: How boys of color develop close peer mentoring relationships

The aim of this study was to investigate the processes involved in developing close peer mentoring relationships among African American and Latino male adolescents in a school-based, group peer mentoring program. Qualitative one-on-one in-depth interviews were conducted with six school staff members, who administer the program, and 26 program participants about their experiences in the mentoring program. Data analysis revealed five program processes that led to close mentoring relationships: (a) rapport-building activities, (b) safe space, (c) mutual support, (d) group identity, and (e) trust. These processes ultimately led to bonding and friendship among program members, which further solidified the previous processes. Implications and future directions are discussed.     

Alterations in immunological and neurological gene expression patterns in Alzheimer's disease tissues

Microarray technology was utilized to isolate disease-specific changes in gene expression by sampling across inferior parietal lobes of patients suffering from late onset AD or non-AD-associated dementia and non-demented controls. Primary focus was placed on understanding how inflammation plays a role in AD pathogenesis. Gene ontology analysis revealed that the most differentially expressed genes related to nervous system development and function and neurological disease followed by genes involved in inflammation and immunological signaling. Pathway analysis also implicated a role for chemokines and their receptors, specifically CXCR4 and CCR3, in AD. Immunohistological analysis revealed that these chemokine receptors are upregulated in AD patients. Western analysis demonstrated an increased activation of PKC, a downstream mediator of chemokine receptor signaling, in the majority of AD patients. A very specific cohort of genes related to amyloid beta accumulation and clearance were found to be significantly altered in AD. The most significantly downregulated gene in this data set was the endothelin converting enzyme 2 (ECE2), implicated in amyloid beta clearance. These data were subsequently confirmed by real-time PCR and Western blot analysis. Together, these findings open up new avenues of investigation and possible therapeutic strategies targeting inflammation and amyloid clearance in AD patients.     

Clean or Dirty? A Systematic Review of Splash Basin Use and Its Infectious Potential in Orthopaedic Surgery

BackgroundSplash basins are used in orthopaedic surgery cases to wash and hold instrumentsintraoperatively. This systematic review aims to summarize information on contamination of splash basins intraoperatively.MethodsA systematic review was conducted using the following search terms: “splash basin” or “splash bucket.” Two authors independently reviewed the literature. Studies were included if they reported on intraoperative splash basin contamination rates. Studies were excluded if they were not relevant to orthopaedic surgery, non-English articles, or repeat studies yielded by different online databases.ResultsThere were seven studies included in this review. The median contamination rate of sterile water or physiologic saline splash basins was 23.9% [range: 2%-74%]. The addition of surgical antiseptics to sterile water splash basins was associated with 0% contamination rates in two studies. The most frequent splash basin contaminants identified in bacterial culture were coagulase negative staphylococcus (50%) and staphylococcus aureus (10%).ConclusionThe splash basin appears to be a frequent source of contamination in the operating room. Many studies suggest abandoning splash basin use altogether, although the efficacy of alternative methods such as cleaning instruments with lap pads in avoiding contamination of the sterile field has not been studied. Further investigation into surgical teams’ use of the splash basin and the contents of the splash basin as they relate to contamination rates may help advance our understanding of optimal use of this surgical tool. Shorter case durations and dilute surgical antiseptics in splash basins appear associated with lower splash basin contamination risk. Level of Evidence: V     

Complicated and fatal Strongyloides infection in Canadians: risk factors,diagnosis and management

STRONGYLOIDIASIS, WHICH IS CAUSED by the nematode Strongyloides stercoralis, is a common and persistent infection, particularly in developing countries. In the setting of compromised cellular immunity, it can result in fulminant dissemination with case-fatality rates of over 70%. The majority of new Canadian immigrants come from countries where Strongyloides is highly endemic; therefore, the burden of Strongyloides may be underappreciated in Canada. Because early diagnosis and therapy can have a marked impact on disease outcome, screening for this infection should be considered mandatory for patients who have a history of travel or residence in a disease-endemic area and risk factors for disseminated disease (e.g., corticosteroid use and human T-lymphotropic virus type I infection). The following case is typical of a Strongyloides infection presenting to an infectious diseases service at a tertiary care hospital: A 50-year-old man who was originally from Cambodia but who had lived in Canada for the past 15 years presented with nausea and vomiting. His history was notable for arthritis, which was treated with prednisone, and type 2 diabetes mellitus. After admission, the patient became febrile and hypotensive. Blood cultures were positive for a gram-negative bacillus, and he was given ciprofloxacin and ceftriaxone. His respiratory status deteriorated, and Strongyloides larvae were incidentally noted on Gram stain and culture after bronchoalveolar lavage (Fig. 1). The patient was given 400 mg of albendazole twice a day and 15 mg of ivermectin once daily, but progressive respiratory failure followed and he died 3 weeks later.Open in a separate windowFig. 1: Strongyloides stercoralis larva tracks on a blood agar plate from the bronchoalveolar lavage of a patient with disseminated strongyloidiasis.This case exemplifies 2 key points. Foremost is that delays in establishing the diagnosis of strongyloidiasis can result in disseminated and fatal infection. Although the gastrointestinal tract is the primary site of Strongyloides infection, associated symptoms such as abdominal pain and intermittent diarrhea may be vague; if ignored by the clinician, the diagnosis may be made only upon dissemination and clinical deterioration of the patient. Second, eliciting an appropriate travel and migration history from patients and recognizing risk factors for disseminated infection are the essential epidemiologic clues for establishing early diagnosis. The purpose of this article is to highlight the risk factors and clinical presentation of strongyloidiasis and to provide a strategy for diagnosis and management. The goal is to raise awareness of this relatively common infection and thereby to facilitate early diagnosis and treatment of this potentially fatal but eminently curable disease.     

Similarity of Cortical Activity Patterns Predicts generalization Behavior

Humans and animals readily generalize previously learned knowledge to new situations. Determining similarity is critical for assigning category membership to a novel stimulus. We tested the hypothesis that category membership is initially encoded by the similarity of the activity pattern evoked by a novel stimulus to the patterns from known categories. We provide behavioral and neurophysiological evidence that activity patterns in primary auditory cortex contain sufficient information to explain behavioral categorization of novel speech sounds by rats. Our results suggest that category membership might be encoded by the similarity of the activity pattern evoked by a novel speech sound to the patterns evoked by known sounds. Categorization based on featureless pattern matching may represent a general neural mechanism for ensuring accurate generalization across sensory and cognitive systems.     

Amino-caprolactam derivatives as gamma-secretase inhibitors

A series of amino-caprolactam sulfonamides were developed from a screening hit. Compounds with good in vitro and in vivo gamma-secretase activity are reported.     

CD2AP regulates SUMOylation of CIN85 in podocytes

Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown that full-length CIN85 is upregulated in podocytes in the absence of CD2AP, whereas in wild-type cells, full-length CIN85 is not detectable. In this study, we show that full-length CIN85 is postranslationally modified by SUMOylation in wild-type podocytes. We can demonstrate that CIN85 is SUMOylated by SUMO-1, -2, and -3 and that SUMOylation is enhanced in the presence of CD2AP. Conversion of lysine 598 to arginine completely abolishes SUMOylation and leads to increased binding of CIN85 to nephrin. Our results indicate a novel role for CD2AP in regulating posttranslational modification of CIN85.