Melanization of verticillium dahliae at the cellular level, 1982

Microsclerotia are thick-walled, large globose cells which serve as survival structures in Verticillium dahliae. The globose cells are characteristic of older hyphal regions. The wild-type strain produces melanin which can be observed within and on the wall of the microsclerotia and extracellular fibers. Fungal melanin is considered necessary for the survival of microsclerotia during long periods of unfavorable conditions. In order to examine the formation of microsclerotia as related to melanin production in wild-type (t-9), the albino-1 microsclerotia (alm-1) and the brown-1 microsclero�tia (brm-1) mutants were grown on potato dextrose agar (PDA) over-laid with cellophane or polygalacturonic acid medium (PGAM) which induces synchronous development of microsclerotia. Albino-1 was induced to produce melanin by a brown substance (scytalone) in the culture filtrate of brm-1 mutant. Scytalone-induced albino (s-alm-1) was compared cytologically with the development of melanin in t-9. Observations were made by phase contrast and trans-mission electron microscopy. The cellular changes that accompanied the change of alm-1 to s-alm-1 were frequently observed mitochondria along with single and double membrane vesicles. There were electron-dense melanin granules similar to t-9 observed within extracellular fibers and on the wall of micro- sclerotia. The precipitate from the 3,3'-diaminobenzidine reaction was demonstrated on the inner mitochondrial mem�brane of alm-1, while s-alm-1 showed activity on the inner and outer mitochondrial membranes. The above mentioned changes in organellar structures and arrangement suggest a correlation with the production of melanin as seen in the wild type

Adenosine, Lidocaine and Magnesium (ALM) therapy modulates early sex-specific inflammatory and immune responses following experimental anterior cruciate ligament rupture and reconstruction

Background: Early dysregulation of local and systemic inflammatory and immune responses is implicated in the pathogenesis of fibrotic and degenerative complications after anterior cruciate ligament reconstruction (ACLR) surgery. In other surgical trauma models, ALM therapy has been shown to blunt inflammation, leading to a more permissive healing environment in injured tissues. The purpose of this study was to evaluate sex-specific effects of surgery and perioperative ALM therapy on leukocyte mobilization and activation, and systemic and joint tissue inflammation in a rat model of ACL rupture and reconstruction. Methods: Adult male and female Sprague–Dawley rats were randomly divided into ALM (male, n = 15; female, n = 14) or Saline control (male, n = 13; female, n = 14) treatment groups. Three days after non-invasive ACL rupture, ACLR surgery was performed on the injured knee. Animals received a 1 h perioperative IV ALM or saline drip, and a 0.1 ml IA bolus of ALM or saline, and were monitored to 120 h postoperative. Hematology, leukocyte immunophenotyping, plasma and synovial inflammatory mediator concentrations, and joint tissue histopathology and gene expression of inflammatory markers were assessed. Results: Following ACLR surgery, plasma concentrations of inflammatory cytokines IL-6, TNF-α and IL-1β peaked later and at a higher magnitude in females compared to males, with ALM dampening this systemic inflammatory response. At 1 h postoperative, ALM boosted circulating B cell numbers in males and females, and decreased neutrophil activation in females. By 72 h, numbers of circulating T cells with immunoregulatory potential were increased in all ALM-treated animals compared to Saline controls, and corresponded to a significant reduction in synovial TNF-α concentrations within the operated knees. Sex-specific treatment differences were found in inflammatory and immune profiles in the synovial fluid and joint tissues. Inflammatory cell infiltration and gene expression of markers of inflammation (Nfκb, Nlrp3), cytoprotective responses (Nrf2), and angiogenesis (Vegf ) were increased in joint synovial tissue from ALM-treated males, compared to controls. In females, ALM treatment was associated with increased mononuclear cell recruitment, and expression of M2 macrophage marker (Arg1) in joint synovial tissue

Interaction of Skeletal and Left Ventricular Mass in Older Adults with Low Muscle Performance

BACKGROUND: It was recently hypothesized the existence of “cardiac-skeletal muscle axis.” However, the relationship between skeletal muscle mass (SMM) and left ventricular mass (LVM) has never been investigated in the specific group of older individuals with low skeletal mass and physical performance. We tested this hypothesis in the SPRINT-T (Sarcopenia and Physical Frailty IN older people: multicomponenT Treatment strategies Trial) population using LVM as independent variable and SMM as dependent variable. METHODS: SMM was assessed by dual-energy X-ray absorptiometry scan and expressed as appendicular lean mass (ALM), and LVM was estimated through echocardiography. Low ALM was defined according to Foundation for the National Institutes of Health Sarcopenia Project criteria, and Short Physical Performance Battery (SPPB) was used to assess physical performance.RESULTS: The population consisted of 100 persons (33 men and 67 women), aged 70 years or older (mean age = 79 5 years) with low ALM and SPPB ranged between 3 and 9, suggestive of physical frailty. Charlson Comorbidity Index median score was 0. Mean value of LVM was 193 67 g, indexed LVM/body surface area (LVM/BSA) was 112 33 g/m2, and cardiac output (CO) was 65 19 L/min. ALM was strongly and positively correlated with LVM (r = 0.54602; P < .0001), LVM/BSA (r = 0.30761; P < .002), CO (r = 0.49621; P < .0001), body mass index (BMI) (r = 0.52461; P < .0001), sex (r = 0.77; P < .001), fat mass (r = 0.38977; P < .0001), and hemoglobin (Hb) (r = 0.26001; P < .01). In the multivariate analysis, LVM (β = .019 .005; P < .0001), CO (β = .038 .016; P = .019), BMI (β = .286 .051; P < .0001), and Hb (β = .544 .175; P = .0025) remained associated to ALM. CONCLUSIONS: In a sample of older persons with low muscle mass and physical performance, LVM was positively and significantly correlated with ALM, independently from blood pressure, physical activity, and other potential confounders. Future studies are needed to address the effect of interventions targeting LVM and SMM

Sarcopenic obesity and reduced BMD in young men living with HIV: body composition and sex steroids interplay

Purpose Sex steroids play a key role on male bone homeostasis and body composition (BC), their role in men living with HIV (MLWH) is less recognized. This study aimed at investigating the prevalence of low BMD, sarcopenia, and sarcopenic obesity (SO) and their relationship with sex steroids in MLWH aged < 50. Methods Prospective, cross-sectional, observational study on MLWH younger than 50 (median age 47.0 years). BC and BMD were evaluated with DXA. Two different definitions of sarcopenia were applied: appendicular lean mass/height(2) (ALMI) < 7.26 kg/m(2) or appendicular lean mass/body weight (ALM/W) < 28.27%. Low BMD was defined for Z-score < -2.0. Sarcopenia coupled with obesity identified SO. Serum total testosterone (T) and estradiol (E2) were measured by LC-MS/MS; free testosterone (cFT) was calculated by Vermeulen equation. Results Sarcopenia was detected in 107 (34.9%) and 44 (14.3%) out of 307 MLWH according to ALMI and ALM/W, respectively. The prevalence of SO was similar by using both ALMI (11.4%) and ALM/W (12.4%). Sarcopenic and SO MLWH had lower total T and cFT in both the definition for sarcopenia. BMD was reduced in 43/307 (14.0%). Serum E2 < 18 pg/mL was an independent contributing factor for sarcopenia, SO, and low BMD. Conclusions T and E2 are important determinants of BC even in MLWH. This is among the first studies investigating the distribution of obesity phenotypes and the prevalence of SO among MLWH showing that SO is present in 11-12% of enrolled MLWH regardless of the definition used. However, deep differences emerged using two different diagnostic definitions

High Prevalence of Sarcopenia in Women with Osteoporotic Fractures

The aim of the present study was to assess the prevalence of sarcopenia in women with osteopenia/osteoporosiswith or without fragility fractures.Patients and methods: 112 ambulatory women with osteopenia/osteporosis were included. Body composition wasdetermined by DXA. Weight, height, body mass index (BMI), bone mineral density (BMD) of the total skeleton, totallean mass (LM), appendicular lean mass (ALM) and the index: appendicular lean mass/height² (ALM/h²) weredetermined. Grip strength and self-selected gait speed were assessed. Results: Average (X ± SD) results were: age70.9 ± 8.2 years, BMI: 23.1 ± 3.3 kg/h², total skeleton BMD T-Score:-1.7 ± 0.8, total LM 33.3 ± 3.8 kg, ALM 14.4 ±2.1kg and ALM/h²: 5.86 ± 0.68 kg/h². Walking speed 0.96±0.21m/s and handgrip: 18.8 ± 4.8 kg. The prevalence ofsarcopenia was: 24.7% (International Working Group criteria). Values for BMI, LM, ALM, ALM/h², gait speed andhand grip were significantly lower in sarcopenic vs. non-sarcopenic patients. 29 patients, average age: 70.5 ± 8.0years had osteoporotic fragility fractures (Fx). The prevalence of sarcopenia in the group of patients with Fx was41.4% vs. 19.3% in the non-Fx patients (n=83) (p<0.018).Conclusion: The prevalence of sarcopenia in women with osteopenia/osteoporosis was higher compared to thatusually reported in non-selected patients of similar age. Those with bone fractures had a significantly higherprevalence of sarcopenia compared to the non-fracture patients. The assessment of muscle mass and function inpatients with osteopenia/osteoporosis is recommended.Fil: Fernández, Candela. Centro de Osteopatías Médicas Dr Mautalen; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Bagur, Alicia Cristina. Centro de Osteopatías Médicas Dr Mautalen; ArgentinaFil: Gomez Glorioso, Dolores. Centro de Osteopatías Médicas Dr Mautalen; ArgentinaFil: González, Diana. Centro de Osteopatías Médicas Dr Mautalen; ArgentinaFil: Mastaglia, Silvina Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Mautalen, Carlos Alfredo. Centro de Osteopatías Médicas Dr Mautalen; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Diet, functional performance and muscle quality of independent-living men and women aged 65-75 years

Age-related sarcopenia is a syndrome characterised by progressive decline in skeletal muscle mass and strength (von Haehling, Morley, & Anker, 2010). The European Working Group on Sarcopenia in Older People recommends the measurement of muscle mass and function as means of diagnosing sarcopenia (Cruz-Jentoft et al., 2010) since sole focus on measurement of muscle mass may be of limited value. The age-associated loss of muscle strength (Dynapenia) cannot be only explained by reductions in muscle size since reductions in strength are more rapid than reductions in muscle (Clark & Manini, 2012). Cawthon et al. (2014) developed cut points for appendicular lean mass (ALM) that would identify individuals with clinically significant weakness taking into account both ALM and strength. Since sarcopenia is a multifaceted syndrome with potentially modifiable factors such as dietary intakes, the aim of this pilot study was to explore the interrelationships between dietary intakes, ALM, and strength. Twenty-five healthy older adults including both female (n=15, age: 68.8 ± 2.9 years) and male (n =10, age 69.5 ± 2.5 years) participants completed a 7-day diet diary before having their handgrip strength and body composition (dual energy X-ray absorptiometry) measured. Males with ALM<19.75 kg and females with ALM<15.02 kg were defined as having low lean muscle mass, whilst cut points of <30 kg and <20 kg (Campbell & Vallis, 2014) were used to identify males and females with low strength. Participants received guidance on recording food and drink by household measures. Energy expenditure was calculated using the World Health Organization/Food and Agriculture Organization equation (Frankenfield, Roth-Yousey, & Compher, 2005) for resting energy expenditure and an activity factor of 1.5. Forty percent (40%) of the females displayed low muscle strength while their male counterparts were all above the 30 kg cut point. ALM was 25.6±3.7 and 15.9±1.7 kg for males and females respectively. Twenty-seven percent (27%) of the females were below the cut point for low lean mass whilst males were all above the equivalent cut point. Energy intake (EI) was 1753±366 kcal for males and 1376±270 kcal for females corresponding to an EI deficit of 27.8±21.7 % and 27.7±6 % for males and females respectively. EI was significantly (P<0.05) lower than recommended EI. Protein intake was 0.97±0.3 g·kg·d-1 for the males and 0.95±0.2 g·kg·d-1 for the females representing 18.8±3.1 and 17.8±2.4 % of EI for males and females respectively. Our findings suggest that females in early retirement years are at greater risk of sarcopenia and dynapenia than their male counterparts. Inadequate energy intake and protein consumption which was below current research led recommendations of 20 % suggest that females may benefit from dietary interventions that would address energy and protein deficits. References Campbell, T. M., & Vallis, L. A. (2014). Predicting fat-free mass index and sarcopenia in assisted-living older adults. Age (Dordr), 36(4), 9674. doi: 10.1007/s11357-014-9674-8 Cawthon, P. M., Peters, K. W., Shardell, M. D., McLean, R. R., Dam, T.-T. L., Kenny, A. M., . . . Guralnik, J. M. (2014). Cutpoints for low appendicular lean mass that identify older adults with clinically significant weakness. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69(5), 567-575. Clark, B. C., & Manini, T. M. (2012). What is dynapenia? Nutrition, 28(5), 495-503. doi: 10.1016/j.nut.2011.12.002 Cruz-Jentoft, A. J., Baeyens, J. P., Bauer, J. M., Boirie, Y., Cederholm, T., Landi, F., . . . European Working Group on Sarcopenia in Older, P. (2010). Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing, 39(4), 412-423. doi: 10.1093/ageing/afq034 Frankenfield, D., Roth-Yousey, L., & Compher, C. (2005). Comparison of predictive equations for resting metabolic rate in healthy nonobese and obese adults: a systematic review. J Am Diet Assoc, 105(5), 775-789. doi: 10.1016/j.jada.2005.02.005 Morley, J. E. (2008). Sarcopenia: diagnosis and treatment. J Nutr Health Aging, 12(7), 452-456. von Haehling, S., Morley, J. E., & Anker, S. D. (2010). An overview of sarcopenia: facts and numbers on prevalence and clinical impact. J Cachexia Sarcopenia Muscle, 1(2), 129-133. doi: 10.1007/s13539-010-0014-

Alemtuzumab: the mechanisms of differential sensitivity and resistance

Alemtuzumab (ALM) is a cytotoxic monoclonal antibody that is used as a therapeutic agent in a variety of clinical settings. The target antigen for ALM is CD52, which is highly expressed on the membrane of mature lymphocytes, but not or only marginally on hematopoietic stem cells, red blood cells, and non-hematopoietic tissues. As such, ALM can be administered for the purpose of lymphocyte depletion with no or only minimal toxicity to other tissues. In this thesis, the mechanism of action of ALM was investigated in the context of two clinical settings, i.e. T-cell depletion before allogeneic stem cell transplantation (alloSCT) and depletion of malignant cells in B lymphoblastic leukemia (B-ALL).LUMC / Geneeskund

Spontaneous breaking of rotational symmetry in superconductors

We show that homogeneous superconductors with broken spin/isospin symmetry lower their energy via a transition to a novel superconducting state where the Fermi-surfaces are deformed to a quasi-ellipsoidal form at zero total momentum of Cooper pairs. In this state, the gain in the condensation energy of the pairs dominates over the loss in the kinetic energy caused by the lowest order (quadrupole) deformation of Fermi-surfaces from the spherically symmetric form. There are two energy minima in general, corresponding to the deformations of the Fermi-spheres into either prolate or oblate forms. The phase transition from spherically symmetric state to the superconducting state with broken rotational symmetry is of the first order.Comment: 5 pages, including 3 figures, published versio

Critical Enhancement of the In-medium Nucleon-Nucleon Cross Section at low Temperatures

The in-medium nucleon-nucleon cross section is calculated starting from the thermodynamic T-matrix at finite temperatures. The corresponding Bethe-Salpeter-equation is solved using a separable representation of the Paris nucleon-nucleon-potential. The energy-dependent in-medium N-N cross section at a given density shows a strong temperature dependence. Especially at low temperatures and low total momenta, the in-medium cross section is strongly modified by in-medium effects. In particular, with decreasing temperature an enhancement near the Fermi energy is observed. This enhancement can be discussed as a precursor of the superfluid phase transition in nuclear matter.Comment: 10 pages with 4 figures (available on request from the authors), MPG-VT-UR 34/94 accepted for publication in Phys. Rev.