Establishment of resistance to Leishmania major infection in susceptible BALB/c mice requires parasite-specific CD8+ T cells

Although CD4+ T cells are generally accepted to be responsible for the determination of resistance to infection in experimental murine cutaneous leishmanlasis, a contribution of CD8+ lymphocytes to immunity can be demonstrated under certain well-defined conditions. Normally highly susceptible BALB/c mice can be rendered resistant to infection with Leishmania major promastigotes by a single injection of monoclonal anti-CD4 antibodies at the beginning of infection. Mice treated in such a way can heal their primary cutaneous lesions and acquire immunity to subsequent challenge infection. Both the resolution of the primary infection and the induced state of immunityto reinfection in these mice is shown to be dependent upon the anti-leishmanial effector functions of CD8+ T cells. Furthermore, in contrast to control infected BALB/c mice, which are unable to mount a delayed-type hypersensitivity (DTH) response to viable parasites, mice cured as a result of treatment with anti-CD4 antibodies in vivo exhibit a strong DTH response, which can be significantly reduced by injection of either anti-CD4 or anti-CD8 monoclonal antibodies prior to antigenic challenge with viable promastigotes. Moreover, increased numbers of specific CD8+ T cells, able to transferLeishmania-specific DTH responses, were found in lymphold organs of BALB/c mice rendered resistant to infection by immunointervention with anti-CD4 monoclonal antibodies at the beginning of infection. Neutralization in vivo of interleukin 4 during the course of infection in BALB/c mice also enables these otherwise susceptible mice to resolve their cutaneous lesions and to decrease the parasite burden in infected tissues. CD8+ T cells are required for both of these beneficial effects. Taken together, these results indicate that in the immune BALB/c mouse, as in the normally resistant CBA mouse, CD8+ lymphocytes are involved in the elimination of L. major and in the establishment and maintenance of immunity against infection with this parasit

Eine gelebte Partizipation ist mehr!

Partizipation im Kleinen leben: Schülerparlament, Themenwahl, Wochenplan, Atelierhalbtage, Klassenrat sowie spontane Programmänderungen aufgrund von Anliegen seitens der Schülerinnen und Schüler. Die Liste, in welchem Rahmen Partizipation von Kindern und Jugendlichen möglich ist, kann fast endlos fortgesetzt werden. Das Zentrum für Schulentwicklung der PH Zürich hat sich vertieft mit Schülerinnen- und Schülerpartizipation im Kanton Zürich auseinandergesetzt.+repphzhbib2018

Signal, Not Poison—Screening Mint Essential Oils for Weed Control Leads to Horsemint

Weed control tries to suppress competitors for a crop and often relies on differential intoxication, making use of differences in uptake, development, or metabolism. We explored the possibility of using natural signals to shift competition in favour of the crop. Using the competitive horsemint (Mentha longifolia) as a paradigm, we showed that essential oils from certain mint species suppress the seedling development of different target species in a specific and efficient manner. The specificity concerned both the donor and the receptor. We demonstrated further that the effect of horsemint oil was specific for actin filaments, and not for microtubules. Since the elimination of actin will impair auxin transport, which is essential for root regeneration in vegetatively propagating weeds, we tested the efficacy of horsemint essential oil in combination with a slow-release carrier against field bindweed (Convolvulus arvensis), a pertinent weed in organic cereal production. We observed that the development of this weed can be specifically blocked, especially if the carrier is worked into the soil. We propose that allelopathic interactions, often relying on manipulative chemical signalling, harbour significant potential for organic weed control

Measuring star formation in high-z massive galaxies: A mid-infrared to submillimeter study of the GOODS NICMOS Survey sample

We present measurements of the mean mid-infrared-to-submillimeter flux densities of massive (M\ast \approx 2 \times 10^11 Msun) galaxies at redshifts 1.7 < z < 2.9, obtained by stacking positions of known objects taken from the GOODS NICMOS Survey (GNS) catalog on maps: at 24 {\mu}m (Spitzer/MIPS); 70, 100, and 160{\mu}m (Herschel/PACS); 250, 350, 500{\mu}m (BLAST); and 870{\mu}m (LABOCA). A modified blackbody spectrum fit to the stacked flux densities indicates a median [interquartile] star-formation rate of SFR = 63 [48, 81] Msun yr^-1 . We note that not properly accounting for correlations between bands when fitting stacked data can significantly bias the result. The galaxies are divided into two groups, disk-like and spheroid-like, according to their Sersic indices, n. We find evidence that most of the star formation is occurring in n \leq 2 (disk-like) galaxies, with median [interquartile] SFR = 122 [100,150] Msun yr^-1, while there are indications that the n > 2 (spheroid-like) population may be forming stars at a median [interquartile] SFR = 14 [9,20] Msun yr^-1, if at all. Finally, we show that star formation is a plausible mechanism for size evolution in this population as a whole, but find only marginal evidence that it is what drives the expansion of the spheroid-like galaxies.Comment: Accepted by MNRAS. 10 pages, 3 figures, 3 table

Cutaneous leishmaniasis in a newly established treatment centre in the Lay Gayint district, Northwest Ethiopia

Background: Cutaneous leishmaniasis (CL) is a neglected tropical disease that primarily affects the most vulnerable populations. In Ethiopia, where this study took place, CL is an important health problem, however, the incidence of CL is poorly monitored. Objectives: This study took place in a recently established CL treatment centre, at Nefas Mewcha Hospital, Lay Gayint. This area was considered to be endemic for CL, however, no cases of CL from Lay Gayint had previously been officially reported to the Amhara Regional Health Bureau. Methods: Following a CL awareness campaign, a retrospective data review was performed of patients presenting to this centre between July 2019 and March 2021. Basic demographic and clinical data were collected by a nurse and recorded in the logbook of the CL treatment centre. Results: Two hundred and one patients presented for diagnosis and treatment. The age of the patients ranged from 2 to 75 years and 63.2% were males. Most patients were between 10- and 19-years-old. The majority (79.1%) of the patients presented with localised cutaneous leishmaniasis and 20.9% with mucocutaneous leishmaniasis. 98% of the patients tested positive for Leishmania parasites by microscopy. Conclusions: This work underpinned how CL is a major public health problem in the Lay Gayint district. It also shows that raising awareness about CL in the community and providing diagnosis and treatment encouraged patients to travel to seek diagnosis and treatment

Influence of neutropenia on mortality of critically ill cancer patients : results of a meta-analysis on individual data

Background: The study objective was to assess the influence of neutropenia on outcome of critically ill cancer patients by meta-analysis of individual data. Secondary objectives were to assess the influence of neutropenia on outcome of critically ill patients in prespecified subgroups (according to underlying tumor, period of admission, need for mechanical ventilation and use of granulocyte colony stimulating factor (G-CSF)). Methods: Data sources were PubMed and the Cochrane database. Study selection included articles focusing on critically ill cancer patients published in English and studies in humans from May 2005 to May 2015. For study selection, the study eligibility was assessed by two investigators. Individual data from selected studies were obtained from corresponding authors. Results: Overall, 114 studies were identified and authors of 30 studies (26.3% of selected studies) agreed to participate in this study. Of the 7515 included patients, three were excluded due to a missing major variable (neutropenia or mortality) leading to analysis of 7512 patients, including 1702 neutropenic patients (22.6%). After adjustment for confounders, and taking study effect into account, neutropenia was independently associated with mortality (OR 1.41; 95% CI 1.23-1.62; P = 0.03). When analyzed separately, neither admission period, underlying malignancy nor need for mechanical ventilation modified the prognostic influence of neutropenia on outcome. However, among patients for whom data on G-CSF administration were available (n = 1949; 25.9%), neutropenia was no longer associated with outcome in patients receiving G-CSF (OR 1.03; 95% CI 0.70-1.51; P = 0.90). Conclusion: Among 7512 critically ill cancer patients included in this systematic review, neutropenia was independently associated with poor outcome despite a meaningful survival. Neutropenia was no longer significantly associated with outcome in patients treated by G-CSF, which may suggest a beneficial effect of G-CSF in neutropenic critically ill cancer patients

Launch of the Space experiment PAMELA

PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature in a wide energy range protons: 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50 MeV-270 GeV) and search for antimatter with a precision of the order of 10^-8). The experiment, housed on board the Russian Resurs-DK1 satellite, was launched on June, 15, 2006 in a 350*600 km orbit with an inclination of 70 degrees. The detector is composed of a series of scintillator counters arranged at the extremities of a permanent magnet spectrometer to provide charge, Time-of-Flight and rigidity information. Lepton/hadron identification is performed by a Silicon-Tungsten calorimeter and a Neutron detector placed at the bottom of the device. An Anticounter system is used offline to reject false triggers coming from the satellite. In self-trigger mode the Calorimeter, the neutron detector and a shower tail catcher are capable of an independent measure of the lepton component up to 2 TeV. In this work we describe the experiment, its scientific objectives and the performance in the first months after launch.Comment: Accepted for publication on Advances in Space Researc

LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood.

International audienceAutosomal recessive LPIN1 mutations have been recently described as a novel cause of rhabdomyolysis in a few families. The purpose of the study was to evaluate the prevalence of LPIN1 mutations in patients exhibiting severe episodes of rhabdomyolysis in infancy. After exclusion of primary fatty acid oxidation disorders, LPIN1 coding sequence was determined in genomic DNA and cDNA. Among the 29 patients studied, 17 (59%) carried recessive nonsense or frameshift mutations, or a large scale intragenic deletion. In these 17 patients, episodes of rhabdomyolysis occurred at a mean age of 21 months. Secondary defect of mitochondrial fatty oxidation or respiratory chain was found in skeletal muscle of two patients. The intragenic deletion, c.2295-866_2410-30del, was identified in 8/17 patients (47%), all Caucasians, and occurred on the background of a common haplotype, suggesting a founder effect. This deleted human LPIN1 form was unable to complement ∆pah1 yeast for growth on glycerol, in contrast to normal LPIN1. Since more than 50% of our series harboured LPIN1 mutations, LPIN1 should be regarded as a major cause of severe myoglobinuria in early childhood. The high frequency of the intragenic LPIN1 deletion should provide a valuable criterion for fast diagnosis, prior to muscle biopsy

Effect of Contemporary Bariatric Surgical Procedures on Type 2 Diabetes Remission. A Population-Based Matched Cohort Study.

OBJECTIVE: The objective of the study is to evaluate the effect of gastric banding, gastric bypass and sleeve gastrectomy on medium to long-term diabetes control in obese participants with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Matched cohort study using primary care electronic health records from the UK Clinical Practice Research Datalink. Obese participants with type 2 diabetes who received bariatric surgery from 2002 to 2014 were compared with matched control participants who did not receive BS. Remission was defined for each year of follow-up as HbA1c <6.5 % and no antidiabetic drugs prescribed. RESULTS: There were 826 obese participants with T2DM who received bariatric surgery including adjustable gastric banding (LAGB) 220; gastric bypass (GBP) 449; or sleeve gastrectomy (SG) 153; with four procedures undefined. Mean HbA1c declined from 8.0 % before BS to 6.5 % in the second postoperative year; proportion with HbA1c <6.5 % (<48 mmol/mol) increased from 17 to 47 %. The proportion of patients in remission was 30 % in the second year, being 20 % for LAGB, 34 % for GBP and 38 % for SG. The adjusted relative rate of remission over the first six postoperative years was 5.97 (4.86 to 7.33, P < 0.001) overall; for LAGB 3.32 (2.27 to 4.86); GBP 7.16 (5.64 to 9.08); and SG 6.82 (5.05 to 9.19). Rates of remission were maintained into the sixth year of follow-up. CONCLUSIONS: Remission of diabetes may continue for up to 6 years after bariatric surgical procedures. Diabetes outcomes are generally more favourable after gastric bypass or sleeve gastrectomy than LAGB