Clinical significance of monocyte heterogeneity

Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis

Assessment of Cranial Neural Crest Proliferation Patterns between the Redeye Tetra \u3cem\u3eMoenkhausia Sanctaefilomenae\u3c/em\u3e and the Zebrafish \u3cem\u3eDanio Rerio\u3c/em\u3e

Among teleost fishes, there is a substantial amount of diversity regarding craniofacial morphology. This study investigated the cellular processes directing the morphological variations observed in the Meckel’s and ceratohyal cartilages of the zebrafish Danio rerio and the redeye tetra Moenkhausia sanctaefilomenae. Utilizing BrdU incorporation, significant interspecific variations relating to cartilage formation were determined. Specifically, interstitial proliferation was found to be more important for the shaping and subsequent growth of the cartilages in D. rerio than in M. sanctaefilomenae. Correspondingly, the expansion of the pharyngeal arches was more dramatic in M. sanctaefilomenae than in D. rerio. This study demonstrates that differential developmental mechanisms underlie the apparent disparities in craniofacial morphology between these two species of fishes

Defining and characterizing Aflatoxin contamination risk areas for corn in Georgia, USA: Adjusting for collinearity and spatial correlation

Aflatoxin is a carcinogenic toxin to humans and animals produced by mold fungi in staple crops. Surveys of Aflatoxin are expensive, and the results are usually not available for implementing within season mitigation strategies. Identification of high and low risk areas and years is essential to reduce the number of samples analyzed for Aflatoxin concentration. Previously a risk factors approach was developed to determine county level Aflatoxin contamination risk in southern Georgia, but Aflatoxin concentrations and risk factor data were not analyzed simultaneously and all risk factors had equal weight which is unrealistic. In the current paper we propose a regression approach to overcome these problems. Spatial Poisson profile regression identified clusters of counties which have similar Aflatoxin risk and risk factor profiles, whilst explicitly taking into account multicollinearity in the risk factor data and spatial autocorrelation in the Aflatoxin data. This approach allows examination of the utility of different highly correlated variables including remotely sensed data that could give information at the sub-county level. The results identify plausible clusters compared to previous work but also give the relative importance of the risk factors associated with those clusters. The approach also helps show that some factors like well-drained soil behave differently from expectations and irrigation data is not useful

Sharpening graduate skills

It is increasingly recognised that a university education is about much more than gaining technical skills. As important to graduates as their degree classification is their portfolio of softer, transferable skills. Consequently, undergraduates now seek to build such skills as part of their core studies. Significantly, not only do the students report improved skills, they also report greater confidence in utilising these skills

Determining future aflatoxin contamination risk scenarios for corn in Southern Georgia, USA using spatio-temporal modelling and future climate simulations

© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Aflatoxins (AFs) are produced by fungi in crops and can cause liver cancer. Permitted levels are legislated and batches of grain are rejected based on average concentrations. Corn grown in Southern Georgia (GA), USA, which experiences drought during the mid-silk growth period in June, is particularly susceptible to infection by Aspergillus section Flavi species which produce AFs. Previous studies showed strong association between AFs and June weather. Risk factors were developed: June maximum temperatures > 33 °C and June rainfall  33 °C and rainfall < 50 mm increased and then plateaued for both emissions scenarios. The percentage of years thresholds were exceeded was greater for RCP 8.5 than RCP 4.5. The spatial distribution of high-risk counties changed over time. Results suggest corn growth distribution should be changed or adaptation strategies employed like planting resistant varieties, irrigating and planting earlier. There were significantly more counties exceeding thresholds in 2010-2040 compared to 2000-2030 suggesting that adaptation strategies should be employed as soon as possible.Peer reviewe

How lamina-associated polypeptide 1 (LAP1) activates Torsin

Lamina-associated polypeptide 1 (LAP1) resides at the nuclear envelope and interacts with Torsins, poorly understood endoplasmic reticulum (ER)-localized AAA+ ATPases, through a conserved, perinuclear domain. We determined the crystal structure of the perinuclear domain of human LAP1. LAP1 possesses an atypical AAA+ fold. While LAP1 lacks canonical nucleotide binding motifs, its strictly conserved arginine 563 is positioned exactly where the arginine finger of canonical AAA+ ATPases is found. Based on modeling and electron microscopic analysis, we propose that LAP1 targets Torsin to the nuclear envelope by forming an alternating, heterohexameric (LAP1-Torsin)[subscript 3] ring, in which LAP1 acts as the Torsin activator. The experimental data show that mutation of arginine 563 in LAP1 reduces its ability to stimulate TorsinA ATPase hydrolysis. This knowledge may help scientists understand the etiology of DYT1 primary dystonia, a movement disorder caused by a single glutamate deletion in TorsinA.National Institute of General Medical Sciences (U.S.) (Award GM103403)United States. Dept. of Energy. Office of Basic Energy Sciences (Contract DE-AC02-06CH11357

Factorial aerobic scope is independent of temperature and primarily modulated by heart rate in exercising Murray Cod (Maccullochella peelii peelii)

Several previous reports, often from studies utilising heavily instrumented animals, have indicated that for teleosts, the increase in cardiac output ( ) during exercise is mainly the result of an increase in cardiac stroke volume (VS) rather than in heart rate (fH). More recently, this contention has been questioned following studies on animals carrying less instrumentation, though the debate continues. In an attempt to shed more light on the situation, we examined the heart rates and oxygen consumption rates ( ; normalised to a mass of 1 kg, given as ) of six Murray cod (Maccullochella peelii peelii; kg) equipped with implanted fH and body temperature data loggers. Data were determined during exposure to varying temperatures and swimming speeds to encompass the majority of the biological scope of this species. An increase in body temperature (Tb) from 14°C to 29°C resulted in linear increases in (26.67-41.78 μmol min−1 kg−1) and fH (22.3-60.8 beats min−1) during routine exercise but a decrease in the oxygen pulse (the amount of oxygen extracted per heartbeat; 1.28-0.74 μmol beat−1 kg−1). During maximum exercise, the factorial increase in was calculated to be 3.7 at all temperatures and was the result of temperature-independent 2.2- and 1.7-fold increases in fH and oxygen pulse, respectively. The constant factorial increases in fH and oxygen pulse suggest that the cardiovascular variables of the Murray cod have temperature-independent maximum gains that contribute to maximal oxygen transport during exercise. At the expense of a larger factorial aerobic scope at an optimal temperature, as has been reported for species of salmon and trout, it is possible that the Murray cod has evolved a lower, but temperature-independent, factorial aerobic scope as an adaptation to the largely fluctuating and unpredictable thermal climate of southeastern Australia

Hydrogen peroxide-based propulsion and power systems.

Less toxic, storable, hypergolic propellants are desired to replace nitrogen tetroxide (NTO) and hydrazine in certain applications. Hydrogen peroxide is a very attractive replacement oxidizer, but finding acceptable replacement fuels is more challenging. The focus of this investigation is to find fuels that have short hypergolic ignition delays, high specific impulse, and desirable storage properties. The resulting hypergolic fuel/oxidizer combination would be highly desirable for virtually any high energy-density applications such as small but powerful gas generating systems, attitude control motors, or main propulsion. These systems would be implemented on platforms ranging from guided bombs to replacement of environmentally unfriendly existing systems to manned space vehicles

Proteomic profiling of high risk medulloblastoma reveals functional biology

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior