Patients with ALS show highly correlated progression rates in left and right limb muscles.

ObjectiveAmyotrophic lateral sclerosis (ALS) progresses at different rates between patients, making clinical trial design difficult and dependent on large cohorts of patients. Currently, there are few data showing whether the left and right limbs progress at the same or different rates. This study addresses rates of decline in specific muscle groups of patients with ALS and assesses whether there is a relationship between left and right muscles in the same patient, regardless of overall progression.MethodsA large cohort of patients was used to assess decline in muscle strength in right and left limbs over time using 2 different methods: The Tufts Quantitative Neuromuscular Exam and Accurate Test of Limb Isometric Strength protocol. Then advanced linear regression statistical methods were applied to assess progression rates in each limb.ResultsThis report shows that linearized progression models can predict general slopes of decline with good accuracy. Critically, the data demonstrate that while overall decline is variable, there is a high degree of correlation between left and right muscle decline in ALS. This implies that irrespective of which muscle starts declining soonest or latest, their rates of decline following onset are more consistent.ConclusionsFirst, this study demonstrates a high degree of power when using unilateral treatment approaches to detect a slowing in disease progression in smaller groups of patients, thus allowing for paired statistical tests. These findings will be useful in transplantation trials that use muscle decline to track disease progression in ALS. Second, these findings discuss methods, such as tactical selection of muscle groups, which can improve the power efficiency of all ALS clinical trials

Training telescope operators and support astronomers at Paranal

The operations model of the Paranal Observatory relies on the work of efficient staff to carry out all the daytime and nighttime tasks. This is highly dependent on adequate training. The Paranal Science Operations department (PSO) has a training group that devises a well-defined and continuously evolving training plan for new staff, in addition to broadening and reinforcing courses for the whole department. This paper presents the training activities for and by PSO, including recent astronomical and quality control training for operators, as well as adaptive optics and interferometry training of all staff. We also present some future plans.Comment: Paper 9910-123 presented at SPIE 201

Divergent and convergent modes of interaction between wheat and Puccinia graminis f. sp tritici isolates revealed by the comparative gene co-expression network and genome analyses

Citation: Rutter, W. B., Salcedo, A., Akhunova, A., He, F., Wang, S. C., Liang, H. Q., . . . Akhunov, E. (2017). Divergent and convergent modes of interaction between wheat and Puccinia graminis f. sp tritici isolates revealed by the comparative gene co-expression network and genome analyses. Bmc Genomics, 18, 20. doi:10.1186/s12864-017-3678-6Background: Two opposing evolutionary constraints exert pressure on plant pathogens: one to diversify virulence factors in order to evade plant defenses, and the other to retain virulence factors critical for maintaining a compatible interaction with the plant host. To better understand how the diversified arsenals of fungal genes promote interaction with the same compatible wheat line, we performed a comparative genomic analysis of two North American isolates of Puccinia graminis f. sp. tritici (Pgt). Results: The patterns of inter-isolate divergence in the secreted candidate effector genes were compared with the levels of conservation and divergence of plant-pathogen gene co-expression networks (GCN) developed for each isolate. Comprative genomic analyses revealed substantial level of interisolate divergence in effector gene complement and sequence divergence. Gene Ontology (GO) analyses of the conserved and unique parts of the isolate-specific GCNs identified a number of conserved host pathways targeted by both isolates. Interestingly, the degree of inter-isolate sub-network conservation varied widely for the different host pathways and was positively associated with the proportion of conserved effector candidates associated with each sub- network. While different Pgt isolates tended to exploit similar wheat pathways for infection, the mode of plant-pathogen interaction varied for different pathways with some pathways being associated with the conserved set of effectors and others being linked with the diverged or isolate-specific effectors. Conclusions: Our data suggest that at the intra-species level pathogen populations likely maintain divergent sets of effectors capable of targeting the same plant host pathways. This functional redundancy may play an important role in the dynamic of the "arms-race" between host and pathogen serving as the basis for diverse virulence strategies and creating conditions where mutations in certain effector groups will not have a major effect on the pathogen's ability to infect the host

TSG-6 is highly expressed in human abdominal aortic aneurysms

BACKGROUND: The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of proinflammatory forces that result in smooth muscle cell apoptosis, extracellular matrix degradation, and progressive diameter expansion. Additional defects in the antiinflammatory response may also play a role but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent antiinflammatory protein involved in extracellular matrix stabilization and cell migration active in many pathological conditions. Here, we describe its role in AAA formation. METHODS: Blood and/or aortic tissue samples were collected from organ donors, subjects undergoing elective AAA screening, and open surgical AAA repair. Aortic specimens collected were preserved for IHC or immediately assayed after tissue homogenization. Protein concentrations in tissue and plasma were assayed by ELISA. All immune cell populations were assayed using FACS. In vitro, macrophage polarization from monocytes was performed with young, healthy donor PBMCs. RESULTS: TSG-6 was found to be abnormally elevated in both the plasma and aortic wall of patients with AAA compared with healthy and risk-factor matched non-AAA donors. We observed the highest tissue concentration of TSG-6 in the less-diseased proximal and distal shoulders compared with the central aspect of the aneurysm. IHC localized most TSG-6 to the tunica media with minor expression in the tunica adventitia of the aortic wall. Higher concentrations of both M1 and M2 macrophages where also observed, however M1/M2 ratios were unchanged from healthy controls. We observed no difference in M1/M2 ratios in the peripheral blood of risk-factor matched non-AAA and AAA patients. Interesting, TSG-6 inhibited the polarization of the antiinflammatory M2 phenotype in vitro. CONCLUSIONS: AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to the vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation

Canary in the Forest?—Tree mortality and canopy dieback of western redcedar linked to drier and warmer summers

Aim: Forest dieback is increasing from unfavourable climate conditions. Western redcedar (WRC)—a culturally, ecologically and economically important species—has recently experienced anomalously high mortality rates and partial canopy dieback. We investigated how WRC tree growth and dieback responded to climate variability and drought using tree-ring methods. Location: Pacific Northwest, USA. Taxon: Western redcedar (Thuja plicata). Methods: We collected tree cores from three tree health status groups (no canopy dieback, partial canopy dieback, and dead trees) at 11 sites in coastal (maritime climate) and interior (continental climate) WRC populations. From growth rates, we computed four growth indices that assessed the resilience to drought and estimated the year of death. Results: Warmer and drier climate conditions in May/June that extended the annual July-to- September dry season reduced radial growth in 9 of 11 sites (1975–2020). WRC trees recovered growth to pre-drought rates within 3 years when post-drought climate conditions were cooler/wetter than average. However, recovery from drought was slower or absent when warmer/drier conditions occurred during the post-drought recovery period, possibly leading to the recent and widespread mortality across the coastal population. WRC mortality was portended by 4–5 years of declining growth. Annually-resolved mortality in coastal populations predominately occurred in 2017–2018 (80% of sampled dead trees), a period that coincided with exceedingly hot temperatures and the longest regionally dry period from May to September (1970–2020). In interior populations, mortality was dispersed among years but associated with warmer and drier conditions from August to September. Main conclusions: Our findings forewarn that a warming climate and more frequent and severe summer droughts, especially in consecutive years, will likely increase the vulnerability of WRC to canopy dieback and mortality and possibly other drought-sensitive trees in one of the world\u27s largest forest carbon sinks

Atmospheric potential oxygen: New observations and their implications for some atmospheric and oceanic models

Measurements of atmospheric O2/N2 ratios and CO2 concentrations can be combined into a tracer known as atmospheric potential oxygen (APO ≈ O2/N2 + CO2) that is conservative with respect to terrestrial biological activity. Consequently, APO reflects primarily ocean biogeochemistry and atmospheric circulation. Building on the work of Stephens et al. (1998), we present a set of APO observations for the years 1996-2003 with unprecedented spatial coverage. Combining data from the Princeton and Scripps air sampling programs, the data set includes new observations collected from ships in the low-latitude Pacific. The data show a smaller interhemispheric APO gradient than was observed in past studies, and different structure within the hemispheres. These differences appear to be due primarily to real changes in the APO field over time. The data also show a significant maximum in APO near the equator. Following the approach of Gruber et al. (2001), we compare these observations with predictions of APO generated from ocean O2 and CO2 flux fields and forward models of atmospheric transport. Our model predictions differ from those of earlier modeling studies, reflecting primarily the choice of atmospheric transport model (TM3 in this study). The model predictions show generally good agreement with the observations, matching the size of the interhemispheric gradient, the approximate amplitude and extent of the equatorial maximum, and the amplitude and phasing of the seasonal APO cycle at most stations. Room for improvement remains. The agreement in the interhemispheric gradient appears to be coincidental; over the last decade, the true APO gradient has evolved to a value that is consistent with our time-independent model. In addition, the equatorial maximum is somewhat more pronounced in the data than the model. This may be due to overly vigorous model transport, or insufficient spatial resolution in the air-sea fluxes used in our modeling effort. Finally, the seasonal cycles predicted by the model of atmospheric transport show evidence of an excessive seasonal rectifier in the Aleutian Islands and smaller problems elsewhere. Copyright 2006 by the American Geophysical Union