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Aspergillus fumigatus is an important global fungal pathogen of humans. Azole drugs are among the most effective treatments for A. fumigatus infection. Azoles are also widely used in agriculture as fungicides against fungal pathogens of crops. Azole-resistant A. fumigatus has been increasing in Europe and Asia for two decades where clinical resistance is thought to be driven by agricultural use of azole fungicides. The most prevalent mechanisms of azole resistance in A. fumigatus are tandem repeats (TR) in the cyp51A promoter coupled with mutations in the coding region which result in resistance to multiple azole drugs (pan-azole resistance). Azole-resistant A. fumigatus has been isolated from patients in the United States (U.S.), but little is known about its environmental distribution. To better understand the distribution of azole-resistant A. fumigatus in the U.S., we collected isolates from agricultural sites in eight states and tested 202 isolates for sensitivity to azoles. We found azole-resistant A. fumigatus in agricultural environments in seven states showing that it is widespread in the U.S. We sequenced environmental isolates representing the range of U.S. sample sites and compared them with publicly available environmental worldwide isolates in phylogenetic, principal component, and ADMIXTURE analyses. We found worldwide isolates fell into three clades, and TR-based pan-azole resistance was largely in a single clade that was strongly associated with resistance to multiple agricultural fungicides. We also found high levels of gene flow indicating recombination between clades highlighting the potential for azole-resistance to continue spreading in the U.S. IMPORTANCE Aspergillus fumigatus is a fungal pathogen of humans that causes over 250,000 invasive infections each year. It is found in soils, plant debris, and compost. Azoles are the first line of defense antifungal drugs against A. fumigatus. Azoles are also used as agricultural fungicides to combat other fungi that attack plants. Azole-resistant A. fumigatus has been a problem in Europe and Asia for 20 years and has recently been reported in patients in the United States (U.S.). Until this study, we did not know much about azole-resistant A. fumigatus in agricultural settings in the U.S. In this study, we isolated azole-resistant A. fumigatus from multiple states and compared it to isolates from around the world. We show that A. fumigatus which is resistant to azoles and to other strictly agricultural fungicides is widespread in the U.S. [ABSTRACT FROM AUTHOR]

Septins are a family of membrane-associated cytoskeletal guanine-nucleotide binding proteins that play crucial roles in various cellular processes, such as cell division, phagocytosis, and organelle fission. Despite their importance, the evolutionary origins and ancestral function of septins remain unclear. In opisthokonts, septins form five distinct groups of orthologs, with subunits from multiple groups assembling into heteropolymers, thus supporting their diverse molecular functions. Recent studies have revealed that septins are also conserved in algae and protists, indicating an ancient origin from the last eukaryotic common ancestor. However, the phylogenetic relationships among septins across eukaryotes remained unclear. Here, we expanded the list of non-opisthokont septins, including previously unrecognized septins from glaucophyte algae. Constructing a rooted phylogenetic tree of 254 total septins, we observed a bifurcation between the major non-opisthokont and opisthokont septin clades. Within the non-opisthokont septins, we identified three major subclades: Group 6 representing chlorophyte green algae (6A mostly for species with single septins, 6B for species with multiple septins), Group 7 representing algae in chlorophytes, heterokonts, haptophytes, chrysophytes, and rhodophytes, and Group 8 representing ciliates. Glaucophyte and some ciliate septins formed orphan lineages in-between all other septins and the outgroup. Combining ancestral-sequence reconstruction and AlphaFold predictions, we tracked the structural evolution of septins across eukaryotes. In the GTPase domain, we identified a conserved GAP-like arginine finger within the G-interface of at least one septin in most algal and ciliate species. This residue is required for homodimerization of the single Chlamydomonas septin, and its loss coincided with septin duplication events in various lineages. The loss of the arginine finger is often accompanied by the emergence of the α0 helix, a known NC-interface interaction motif, potentially signifying the diversification of septin-septin interaction mechanisms from homo-dimerization to hetero-oligomerization. Lastly, we found amphipathic helices in all septin groups, suggesting that membrane binding is an ancestral trait. Coiled-coil domains were also broadly distributed, while transmembrane domains were found in some septins in Group 6A and 7. In summary, this study advances our understanding of septin distribution and phylogenetic groupings, shedding light on their ancestral features, potential function, and early evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Delic, Shuman, Lee, Bahmanyar, Momany and Onishi.)

Subsurface microorganisms make up the majority of Earth's microbial biomass, but ecological processes governing surface communities may not explain community patterns at depth because of burial. Depth constrains dispersal and energy availability, and when combined with geographic isolation across landscapes, may influence community assembly. We sequenced the 16S rRNA gene of bacteria and archaea from 48 sediment cores across 36 lakes in four disconnected mountain ranges in Wyoming, USA and used null models to infer assembly processes across depth, spatial isolation, and varying environments. Although we expected strong dispersal limitations across these isolated settings, community composition was primarily shaped by environmental selection. Communities consistently shifted from domination by organisms that degrade organic matter at the surface to methanogenic, low-energy adapted taxa in deeper zones. Stochastic processes-like dispersal limitation-contributed to differences among lakes, but because these effects weakened with depth, selection processes ultimately governed subsurface microbial biogeography., (© 2024 John Wiley & Sons Ltd.)

Septin GTPases form nonpolar heteropolymers that play important roles in cytokinesis and other cellular processes. The ability to form heteropolymers appears to be critical to many septin functions and to have been a major driver of the high conservation of many septin domains. Septins fall into five orthologous groups. Members of Groups 1-4 interact with each other to form heterooligomers and are known as the "core septins." Representative core septins are present in all fungi and animals so far examined and show positional orthology with monomer location in the heteropolymer conserved within groups. In contrast, members of Group 5 are not part of canonical heteropolymers and appear to interact only transiently, if at all, with core septins. Group 5 septins have a spotty distribution, having been identified in specific fungi, ciliates, chlorophyte algae, and brown algae. In this review we compare the septins from nine well-studied model organisms that span the tree of life ( Homo sapiens , Drosophila melanogaster , Schistosoma mansoni , Caenorhabditis elegans , Saccharomyces cerevisiae , Aspergillus nidulans , Magnaporthe oryzae , Tetrahymena thermophila , and Chlamydomonas reinhardtii ). We focus on classification, evolutionary relationships, conserved motifs, interfaces between monomers, and positional orthology within heteropolymers. Understanding the relationships of septins across kingdoms can give new insight into their functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shuman and Momany.)

To characterize microbiomes and other ecological assemblages, ecologists routinely sequence and compare loci that differ among focal taxa. Counts of these sequences convey information regarding the occurrence and relative abundances of taxa, but provide no direct measure of their absolute abundances, due to the technical limitations of the sequencing process. The relative abundances in compositional data are inherently constrained and difficult to interpret. The incorporation of internal standards (ISDs; colloquially referred to as 'spike-ins') into DNA pools can ameliorate the problems posed by relative abundance data and allow absolute abundances to be approximated. Unfortunately, many laboratory and sampling biases cause ISDs to underperform or fail. Here, we discuss how careful deployment of ISDs can avoid these complications and be an integral component of well-designed studies seeking to characterize ecological assemblages via sequencing of DNA., (© 2020 John Wiley & Sons Ltd.)

Anthropogenic climate change is continuously altering ecological responses to disturbance and must be accounted for when examining ecological resilience. One way to measure resilience in ecological datasets is by considering the amount and duration of change from a baseline created by perturbations, such as disturbances like wildfire. Recovery occurs when ecological conditions return to equilibrium, meaning that no subsequent changes can be attributed to the effects of the disturbance, but climate change often causes the recovered state to differ from the previous baseline. The palaeoecological record provides an opportunity to examine these expectations because palaeoclimates changed continuously; few periods existed when environmental conditions were stationary. Here we demonstrate a framework for examining resilience in palaeoecological records against the backdrop of a non-stationary climate by considering resilience as two components of (i) resistance (magnitude of change) and (ii) recovery (time required to return) to predicted equilibrium values. Measuring these components of resilience in palaeoecological records requires high-resolution fossil (e.g. pollen) records, local palaeoclimate reconstructions, a model to predict ecological change in response to climate change, and disturbance records measured at the same spatial scale as the ecological (e.g. vegetation history) record. Resistance following disturbance is measured as the deviation of the fossil record from the ecological state predicted by the palaeoclimate records, and recovery time is measured as the time required for the fossil record to return to predicted values. We show that some cases may involve nearly persistent equilibrium despite large climate changes, but that others can involve a shift to a new state without any complete recovery.

We argue that two society-level properties-resistance to change and diversity within a culture-significantly affect agents' degrees of marginalization, which is here defined as access to cultural knowledge and institutional means for accomplishing cultural goals. We develop an agent-based model using findings from Norasakkunkit et al. (Norasakkunkit and Uchida, 2011, 2014; Norasakkunkit et al., 2012). We found that varying the degrees of resistance to change and diversity affected similarities between the mainstream subculture and other subcultures, changes in subcultures over time, and the relative population proportion of each subculture. In particular, we found that high diversity and low resistance to change created the greatest cultural changes within the marginalized subculture over time and allowed for maximal growth of rebellious subcultures. Also, low diversity and high resistance to change allowed for maximal growth of the marginalized subcultures and the greatest overlap between the marginalized and mainstream subcultures. These have important implications for understanding the emergence and maintenance of marginalization in post-industrial societies.

Ecosystems may shift abruptly when the effects of climate change and disturbance interact, and landscapes with regularly patterned vegetation may be especially vulnerable to abrupt shifts. Here we use a fossil pollen record from a regularly patterned ribbon forest (alternating bands of forests and meadows) in Colorado to examine whether past changes in wildfire and climate produced abrupt vegetation shifts. Comparing the percentages of conifer pollen with sedimentary δ 18 O data (interpreted as an indicator of temperature or snow accumulation) indicates a first-order linear relationship between vegetation composition and climate change with no detectable lags over the past 2,500 yr (r = 0.55, P < 0.001). Additionally, however, we find that the vegetation changed abruptly within a century of extensive wildfires, which were recognized in a previous study to have burned approximately 80% of the surrounding 1,000 km 2 landscape 1,000 yr ago when temperatures rose ~0.5°C. The vegetation change was larger than expected from the effects of climate change alone. Pollen assemblages changed from a composition associated with closed subalpine forests to one similar to modern ribbon forests. Fossil pollen assemblages then remained like those from modern ribbon forests for the following ~1,000 yr, providing a clear example of how extensive disturbances can trigger persistent new vegetation states and alter how vegetation responds to climate., (© 2017 by the Ecological Society of America.)

Muscle synergies are typically calculated from electromyographic (EMG) signals using nonnegative matrix factorization. Synergies identify weighted groups of muscles that are commonly activated together during a task, such as walking. Synergy analysis has become an emerging tool to evaluate neuromuscular control; however, the repeatability of synergies between trials and days has not been evaluated. The goal of this study was to evaluate the repeatability of synergy complexity and structure in unimpaired individuals and individuals with cerebral palsy (CP). EMG data were collected from eight lower-limb muscles during gait for six typically developing (TD) children and five children with CP on two separate days, over three walking speeds. To evaluate synergy complexity, we calculated the total variance accounted for by one synergy (tVAF1). On a given day, the average range in tVAF1 between gait cycles was 18.2% for TD and 19.1% for CP. The average standard deviation in tVAF1 between gait cycles was 4.9% for TD and 5.0% for CP. Average tVAF1 calculated across gait cycles was not significantly different between days for TD or CP participants. Comparing synergy structure, the average (standard deviation) within day correlation coefficients of synergy weights for two or more synergies were 0.89 (0.15) for TD and 0.88 (0.15) for CP. Between days, the average correlation coefficient of synergy weights for two or more synergies was greater than 0.89 for TD and 0.74 for CP. These results demonstrate that synergy complexity and structure averaged over multiple gait cycles are repeatable between days in both TD and CP groups., (Copyright © 2016 Elsevier B.V. All rights reserved.)

As the earth system moves to a novel state, model systems (experimental, observational, paleoecological) are needed to assess and improve the predictive accuracy of ecological models under environments with no contemporary analog. In recent years, we have intensively studied the no-analog plant associations and climates in eastern North America during the last deglaciation to better constrain their spatiotemporal distribution, test hypotheses about climatic and megaherbivory controls, and assess the accuracy of species- and community-level models. The formation of no-analog plant associations was asynchronous, beginning first in the south-central United States; at sites in the north-central United States, it is linked to declining megafaunal abundances. Insolation and temperature were more seasonal than present, creating climates currently nonexistent in North America, and shifting species-climate relationships for some taxa. These shifts pose a common challenge to empirical paleoclimatic reconstructions, species distribution models (SDMs), and conservation-optimization models based on SDMs. Steps forward include combining recent and paleoecological data to more fully describe species' fundamental niches, employing community-level models to model shifts in species interactions under no-analog climates, and assimilating paleoecological data with mechanistic ecosystem models. Accurately modeling species interactions under novel environments remains a fundamental challenge for all forms of ecological models., (© 2013 New York Academy of Sciences.)

Interactions among multiple causes of ecological perturbation, such as climate change and disturbance, can produce "ecological surprises." Here, we examine whether climate-fire-vegetation interactions can produce ecological changes that differ in direction from those expected from the effects of climate change alone. To do so, we focus on the "Big Woods" of central Minnesota, USA, which was shaped both by climate and fire. The deciduous Big Woods forest replaced regional woodlands and savannas after the severity of regional fire regimes declined at ca. AD 1300. A trend toward wet conditions has long been assumed to explain the forest expansion, but we show that water levels at two lakes within the region (Wolsfeld Lake and Bufflehead Pond) were low when open woodlands were transformed into the Big Woods. Water levels were high instead at ca. 2240-795 BC when regional fire regimes were most severe. Based on the correlation between water levels and fire-regime severity, we infer that prolonged or repeated droughts after ca. AD 1265 reduced the biomass and connectivity of fine fuels (grasses) within the woodlands. As a result, regional fire severity declined and allowed tree populations to expand. Tree-ring data from the region show a peak in the recruitment of key Big Woods tree species during the AD 1930s drought and suggest that low regional moisture balance need not have been a limiting factor for forest expansion. The regional history, thus, demonstrates the types of counterintuitive ecosystem changes that may arise as climate changes in the future.

Purpose: Cryosurgical ablation of the prostate is 1 approach to the treatment of localized prostate cancer. Third generation cryosurgery uses gas driven probes that allow for a decrease in probe diameter to 17 gauge (1.5 mm). The safety, morbidity and preliminary prostate specific antigen (PSA) results of 122 cases are reported., Materials and Methods: A total of 106 patients have undergone percutaneous cryosurgery using a brachytherapy template with at least 12 months of PSA followup. Immediate and delayed morbidities were evaluated. PSA results at 3 and 12 months were recorded, and failure was defined as the inability to reach a nadir of 0.4 ng/ml or less., Results: Complications in patients undergoing primary cryosurgery included tissue sloughing (5%), incontinence (pads, 3%), urge incontinence/no pads (5%), transient urinary retention (3.3%) and rectal discomfort (2.6%). There were no cases of fistulas or infections. Postoperative impotence was 87% in previously potent patients. For patients who underwent salvage cryosurgery there were no fistulas reported and 2 (11%) patients required pads after salvage cryosurgery. A total of 96 (81%) patients achieved a PSA nadir of 0.4 ng/ml or less at 3 months of followup, while 79 of 106 (75%) remained free from biochemical recurrence at 12 months. A total of 42 (78%) low risk patients (Gleason score 7 or less and PSA 10 or less) remained with a PSA of 0.4 ng/ml or less at 12 months of followup, compared to 37 (71%) high risk patients. All patients were discharged within 24 hours., Conclusions: After a followup of 1 year 3rd generation cryosurgery appears to be well tolerated and minimally invasive. The use of ultrathin needles through a brachytherapy template allows for a simple percutaneous procedure and a relatively short learning curve. A prospective multicenter trial is ongoing to determine the long-term efficacy of this technique.

Platelet activation is an important determinant of acute outcomes of percutaneous intervention. The objective of this study was to assess the effect of rotational atherectomy on platelet activation in an in vitro model. Freshly collected heparinized porcine blood was exposed to a 2.0-mm Rotablator burr rotating at one of three speeds: 180,000, 140,000, or 0 rpm. The specimens were analyzed immediately for concentration and size of platelet aggregates and plasma-free hemoglobin. There were significantly more platelet aggregates of >20-microm diameter at higher speeds (7,434+/-2,193 at 180,000, vs. 2,269+/-627 at 140,000, vs. 633+/-258 aggregates/ml at 0 rpm; P < 0.001). Plasma-free hemoglobin, a simple measure of cell damage, decreased with decreasing rotational speed (429+/-168 mg/dl at 180,000, vs. 88+/-44 mg/dl at 140,000, vs. 9+/-9 mg/dl at 0 rpm; P < 0.0001). In vitro, platelet activation decreases with decreasing burr speed, suggesting that the use of the Rotablator system at its minimum approved speed (140,000 rpm) could prove clinically beneficial.

Rotational atherectomy can generate heat from the friction of the burr as it ablates atherosclerotic plaque. The objective of this study is to correlate Rotablator technique and heat generation using two experimental models. First, 2.0 mm burrs were advanced through a lesion model derived from bovine bone implanted with thermal probes. Intermittent ablation with minimal decelerations resulted in a smaller temperature increase than continuous ablation with maximal decelerations (2.6 +/- 1.3 vs. 13.9 +/- 1.0 degrees C, respectively, P < 0.01). The second model used porcine femoral arteries cradled in constricting polyethylene grafts with thermal probes in contact with the adventitia. As the burr advanced through the segment, RPM decreases of 5-7 k resulted in a temperature rise of 4.1 +/- 1.2 degrees C, whereas decelerations of 10-20 k resulted in a 11.3 +/- 6.2 degrees C temperature increase. We conclude that excessive drops in speed and aggressive advancement of the burr are related to significant increases in temperature and potential thermal injury.

Purpose: Cryosurgical ablation of the prostate has recently received much attention as a therapeutic alternative for the treatment of localized prostatic adenocarcinoma. Biopsies after treatment reveal a variety of dysplastic changes as well as unaltered prostatic glandular epithelial elements. Prostate specific antigen (PSA) remains undetectable in the majority of men. However, in some PSA increases without demonstrable local recurrence., Materials and Methods: A total of 383 patients underwent 447 procedures between June 1990 and January 1994. Of 358 biopsies performed at our institution, 317 (2,075 cores) were available for review. Each core was examined for unaltered prostatic glandular epithelial elements and then scored for the percentage of epithelial glandular involvement according to a scale of: 0-no, 0.5-less than 10%, 1-10 to 25%, 2-25 to 50%, 3-50 to 75% and 4-76 to 100% unaltered prostatic glandular epithelial elements., Results: Of 317 biopsies 158 (49.8%) contained no unaltered prostatic glandular epithelial elements, while 185 (58.3%) and 206 (65%) had 1 core containing 10% and 10 to 25%, respectively, of such elements. Of 262 cases (82.6%) with a mean of 10% unaltered prostatic glandular epithelial elements per core 22 (8.4%) were positive for residual carcinoma. Among 55 cases with more normal epithelium per core 24 (43.6%) were positive for residual carcinoma. Patients with a positive biopsy had a median PSA of 2.02 ng./ml. (average gland/core score 0.54). Median PSA for men with negative biopsies was 0.2 ng./ml. (gland/core score 0.124)., Conclusions: Cryosurgical ablation of the prostate has the ability to ablate prostatic tissue completely, thus rendering it free of glandular elements as determined by biopsy. Increasing PSA can indicate residual glandular elements. Increases in unaltered prostatic glandular epithelial elements with time are not paralleled by increased rates of local disease recurrence. undetectable serum PSA has a low risk of residual unaltered prostatic glandular epithelial elements and localized carcinoma. Results as measured by unaltered prostatic glandular epithelial elements and PSA improve with the surgical experience.

Background: Surgical techniques utilizing the application of very low temperatures to malignant tissues have been used increasingly in recent years in the minimally invasive treatment of prostate cancer. An area of potential application appears to be in the management of radiation resistant prostate cancer., Methods: This study represents a retrospective chart review of 33 patients undergoing cryosurgical ablation of the prostate (CSAP) according to a protocol designed by an institutional review board at a single institution for the treatment of radiation resistant prostate cancer. Radiation resistance was defined as a positive prostate needle biopsy and rising prostate specific antigen (PSA). Treatment effect was assessed by serial post treatment PSA determinations and extensive systematic post treatment prostate needle biopsies., Results: Of the 33 patients analyzed, 24 converted to an all negative biopsy status after one CSAP treatment. Repeat treatment converted two additional patients to a biopsy negative status. CSAP appeared to lower PSA dramatically in most patients. One year after treatment, of 10 patients not on androgen deprivation therapy, 3 maintained a PSA of < 0.4 ng/mL and those patients with androgen deprivation therapy maintained a PSA of < 4.0 ng/mL. The most frequent complications included sloughing syndrome (15.4%) and incontinence (10.3%)., Conclusions: CSAP appears to eliminate biopsy detectable prostate tumor effectively in the majority of cases in the salvage setting following radiation therapy. A significant discrepancy exists, however, between the biopsy "cure" rate and the biochemical "cure" rate, even in the short term. There is a suggestion that early detection of radiation failure may improve results of this salvage therapy.

1. Cryosurgical ablation of the prostate is an attempt to use the proved cytodestructive abilities of cryosurgery in combination with the guidance of transrectal ultrasound to provide local disease control with less morbidity and a quicker recovery period. 2. Cryosurgical ablation of the prostate begins as a same day admission. Patients are out of bed and eating as tolerated that evening. They are generally discharged the following day if able to manage the suprapubic tube. 3. Though the recovery period is generally a quick one, there exist many idiosyncrasies to this recovery which make careful interaction between the physician, nurse, and patient critical.

A model of teaching psychological aspects of infant growth and development to medical students in a pediatric clinical rotation is described. Small groups of 8 to 10 medical students observe an infant developmental-assessment-parent-interview conducted by a child development specialist. Emphasis is placed upon demonstrating infant temperament, age-appropriate competencies, and the dynamic interplay between parent and child. Evaluation of this training program suggests its effectiveness as a method of instruction and its usefulness as an approach to the evaluation of the young child.

This paper reviews recent changes in perspectives of development in the prenatal, neonatal, and infancy periods and describes exemplary preventive interventions and their evaluation. Particular emphasis is placed on expanding criteria for successful early interventions to include measures of socioemotional and physical health as well as the more traditional measures of intellectual development. A theme which emerges is the need for peer and professional support for early parenting.