Transcriptional Heterogeneity and the Microbiome of Cutaneous T-Cell Lymphoma

Cutaneous T-Cell Lymphomas (CTCL) presents with substantial clinical variability and transcriptional heterogeneity. In the recent years, several studies paved the way to elucidate aetiology and pathogenesis of CTCL using sequencing methods. Several T-cell subtypes were suggested as the source of disease thereby explaining clinical and transcriptional heterogeneity of CTCL entities. Several differentially expressed pathways could explain disease progression. However, exogenous triggers in the skin microenvironment also seem to affect CTCL status. Especially Staphylococcus aureus was shown to contribute to disease progression. Only little is known about the complex microbiome patterns involved in CTCL and how microbial shifts might impact this malignancy. Nevertheless, first hints indicate that the microbiome might at least in part explain transcriptional heterogeneity and that microbial approaches could serve in diagnosis and prognosis. Shaping the microbiome could be a treatment option to maintain stable disease. Here, we review current knowledge of transcriptional heterogeneity of and microbial influences on CTCL. We discuss potential benefits of microbial applications and microbial directed therapies to aid patients with CTCL burden

The Learning CART Module: Community Outreach

Today\u27s leaders must understand their role as enablers who help people to change their lives and communities. They must recognize that people are responsible for their own development and rely on non-directive guidance to facilitate community action. Enabling leaders are concerned with coordinated efforts and productive performance by the group they work with and have traits and skills which integrate individual needs into collective goals. Perhaps most importantly, enabling leaders have the ability to develop leadership potential in people. This module seeks to sensitize participants to the complexities of doing effective outreach and to provide them with and understanding of the issues and skills important to initiating community work. The first part of the module gives a broad overview of reaching out to the community. Participants map their own communities and examine issues such as respect and trust in different cultures and their roles as insiders and outsiders in doing outreach. The focus of the second part is more specific and introduces Participatory Action Research (PAR) as a method for implementing community development programs. Community outreach techniques are discussed, and a force field analysis activity highlights the resources and constraints that influence achieving goals

Planting Date, Hybrid Maturity, and Weather Effects on Maize Yield and Crop Stage

Unfavorable weather conditions frequently cause farmers to plant maize (Zea mays L.) outside the optimum planting timeframe. We analyzed maize yield and phenology from a multilocation, year, hybrid relative maturity, and planting date experiment performed in Iowa, USA. Our objectives were to determine the optimum combination of planting date and relative maturity to maximize maize grain yield per environment and to elucidate the risk associated with the use of “full-season hybrids” when planting occurs beyond the optimum planting date. Analysis of variance (ANOVA) attributed 70% of the variability in grain yield to planting date and only 10% to relative maturity indicating that short and full-season hybrid relative maturities produced similar grain yields regardless of when they were planted as long as the crops reached maturity before harvesting. Our analysis indicated time to silking is a good indication of expected yield potential with a critical time (beyond which yield is reduced) to be 23 July for Iowa. Furthermore, we found that a minimum growing degree accumulation of 648°Cday during the grain-filling period maximized maize yield. Overall, this study brings new results to assist decision making regarding planting date by hybrid relative maturity across Iowa

Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children

Early diverging insect-pathogenic fungi of the order entomophthorales possess diverse and unique subtilisin-like serine proteases

Insect-pathogenic fungi use subtilisin-like serine proteases (SLSPs) to degrade chitin-associated proteins in the insect procuticle. Most insect-pathogenic fungi in the order Hypocreales (Ascomycota) are generalist species with a broad host-range, and most species possess a high number of SLSPs. The other major clade of insect-pathogenic fungi is part of the subphylum Entomophthoromycotina (Zoopagomycota, formerly Zygomycota) which consists of high host-specificity insect-pathogenic fungi that naturally only infect a single or very few host species. The extent to which insect-pathogenic fungi in the order Entomophthorales rely on SLSPs is unknown. Here we take advantage of recently available transcriptomic and genomic datasets from four genera within Entomophthoromycotina: the saprobic or opportunistic pathogens Basidiobolus meristosporus, Conidiobolus coronatus, C. thromboides, C. incongruus, and the host-specific insect pathogens Entomophthora muscae and Pandora formicae, specific pathogens of house flies (Muscae domestica) and wood ants (Formica polyctena), respectively. In total 154 SLSP from six fungi in the subphylum Entomophthoromycotina were identified: E. muscae (n = 22), P. formicae (n = 6), B. meristosporus (n = 60), C. thromboides (n = 18), C. coronatus (n = 36), and C. incongruus (n = 12). A unique group of 11 SLSPs was discovered in the genomes of the obligate biotrophic fungi E. muscae, P. formicae and the saprobic human pathogen C. incongruus that loosely resembles bacillopeptidase F-like SLSPs. Phylogenetics and protein domain analysis show this class represents a unique group of SLSPs so far only observed among Bacteria, Oomycetes and early diverging fungi such as Cryptomycota, Microsporidia, and Entomophthoromycotina. This group of SLSPs is missing in the sister fungal lineages of Kickxellomycotina and the fungal phyla Mucoromyocta, Ascomycota and Basidiomycota fungi suggesting interesting gene loss patterns