Acinetobacter baumannii, a Multidrug-Resistant Opportunistic Pathogen in New Habitats: A Systematic Review.

In recent years, humanity has begun to face a growing challenge posed by a rise in the prevalence of antibiotic-resistant bacteria. This has resulted in an alarming surge in fatalities and the emergence of increasingly hard-to-manage diseases. Acinetobacter baumannii can be seen as one of these resilient pathogens due to its increasing prevalence in hospitals, its resistance to treatment, and its association with elevated mortality rates. Despite its clinical significance, the scientific understanding of this pathogen in non-hospital settings remains limited. Knowledge of its virulence factors is also lacking. Therefore, in this review, we seek to shed light on the latest research regarding the ecological niches, microbiological traits, and antibiotic resistance profiles of Acinetobacter baumannii. Recent studies have revealed the presence of this bacterium in a growing range of environmental niches, including rivers, treatment plants, and soils. It has also been discovered in diverse food sources such as meat and vegetables, as well as in farm animals and household pets such as dogs and cats. This broader presence of Acinetobacter baumannii, i.e., outside of hospital environments, indicates a significant risk of environmental contamination. As a result, greater levels of awareness and new preventive measures should be promoted to address this potential threat to public health.

The role of interface geometry and appendages on the mesoscale mechanics of the skin.

The skin is the largest organ in the human body and serves various functions, including mechanical protection and mechanosensation. Yet, even though skin's biomechanics are attributed to two main layers-epidermis and dermis-computational models have often treated this tissue as a thin homogeneous material or, when considering multiple layers, have ignored the most prominent heterogeneities of skin seen at the mesoscale. Here, we create finite element models of representative volume elements (RVEs) of skin, including the three-dimensional variation of the interface between the epidermis and dermis as well as considering the presence of hair follicles. The sinusoidal interface, which approximates the anatomical features known as Rete ridges, does not affect the homogenized mechanical response of the RVE but contributes to stress concentration, particularly at the valleys of the Rete ridges. The stress profile is three-dimensional due to the skin's anisotropy, leading to high-stress bands connecting the valleys of the Rete ridges through one type of saddle point. The peaks of the Rete ridges and the other class of saddle points of the sinusoidal surface form a second set of low-stress bands under equi-biaxial loading. Another prominent feature of the heterogeneous stress pattern is a switch in the stress jump across the interface, which becomes lower with respect to the flat interface at increasing deformations. These features are seen in both tension and shear loading. The RVE with the hair follicle showed strains concentrating at the epidermis adjacent to the hair follicle, the epithelial tissue surrounding the hair right below the epidermis, and the bulb or base region of the hair follicle. The regions of strain concentration near the hair follicle in equi-biaxial and shear loading align with the presence of distinct mechanoreceptors in the skin, except for the bulb or base region. This study highlights the importance of skin heterogeneities, particularly its potential mechanophysiological role in the sense of touch and the prevention of skin delamination.

Micronutrient Deficiencies in Older Adults in Latin-America: A Narrative Review.

BACKGROUND: The population in Latin America and Caribbean (LAC) has experienced a major demographic transition with increased numbers of older adults (OA). This change brings opportunities in the public health sector to implement health prevention interventions and delay the onset of geriatric syndromes. Micronutrients play an important role in the maintenance of biological function which contributes to longevity. Micronutrient deficiencies (MD) in OA increase the risk for onset of chronic comorbidities and geriatric syndromes. AIM: To review and summarize the existing data on micronutrient status in OA in the LAC region and discuss the gaps and challenges in public health approaches to address deficiencies. METHODS: Literature review in Medline for records describing nutritional biomarkers in older adults (≥ 60y) from community dwelling and population-based studies in LAC. RESULTS: Few countries (including Chile, Ecuador, Costa Rica, Brazil, and Mexico) have documented one or more nutritional deficiencies for OA in national health surveys, however across the entire region, evidence of micronutrient levels is scarce. Some surveys have documented a high prevalence and large heterogeneity in the prevalence of vitamin D followed by B12 deficiency, being the 2 MDs most studied due their effects on cognition, frailty, and bone mineral density in the OA population. Other MD including C, E, A, copper, zinc, iron, and selenium have also been reported. CONCLUSION: Information on the micronutrient status in OA from LAC is poorly documented. Research and capacity building initiatives in the region are crucial to develop tailored strategies that address the specific nutritional needs and challenges faced by the ageing population in Latin-America.

Plain language titleMicronutrients Deficiencies in Older Adults in Latin AmericanPlain language summaryFor the first time, there are more older adults (OA) than children worldwide. In the Latin America and Caribbean (LAC) region, OA represents 13.2% of the population, and it is projected to increase to 30% (220 millions) by 2030. This demographic shift represents an opportunity in the public health sector to implement health prevention strategies and public health policies to delay the onset of geriatric syndromes in the younger generation. Vitamins and minerals (micronutrients) are necessary in our body to maintain biological function. Deficiencies in older ages have been associated with the onset of geriatric syndromes (such as sarcopenia, frailty, cognitive impairment, and falls, among others). Therefore, it is relevant to understand the magnitude and distribution of micronutrient deficiencies in OA in the LAC region. This will help to inform decision-makers to further implement early actions to maintain good nutrition and health status in the population. In this narrative review, we highlight that few countries in the LAC region documented one or more nutritional deficiencies for OA in their national health surveys. Across the entire region, evidence of micronutrient levels in OA is scarce. Vitamin D and vitamin B12 are the 2 most reported micronutrients in the OA population. Research and capacity-building in the region are crucial to develop tailored strategies to address specific nutritional needs and challenges faced by the aging population in Latin America.

Pooling of six respiratory samples for the detection of SARS-CoV-2: A validation and cost study in a cohort in Lima, Peru.

Background: The continuous evolution of the SARS-CoV-2 pandemic has led to a high demand for diagnostic testing and major shortages in testing materials, especially in low- and middle-income countries. As an alternative to testing individual samples, pooling of respiratory samples has been suggested. Previous studies have assessed performance of pooling, mainly using nasopharyngeal samples for the detection of SARS-CoV-2, but few studies have examined the performance of pooling the more practical nasal swabs or saliva samples. Objective: To evaluate the sensitivity, specificity, and potential cost reduction of pooling of nasal swab (NS) and saliva (SL) samples for detection of SARS-CoV-2 in a community-based cohort study in Lima, Peru. Study design: A prospective cohort study was conducted in a community setting in San Juan de Lurigancho, Lima-Peru. NS and SL samples were collected from 132 participants twice-a-week for a 2-month period. Pools of 2 to 12 samples of the same type, from participants of the same household, were tested by RT-PCR. After pooled testing, all individual samples from positive pools and all individual samples from randomly chosen negative pools were evaluated. For assessment of diagnostic performance, pool testing results were compared with results from individual testing, which served as reference, and concordance in pooled and individual test detections was evaluated. Laboratory costs for both types of samples and testing were compared. Results: A total of 2008 NS and 2002 SL samples were collected from 132 study participants. We tested 329 NS and 333 SL pools. The mean pool size for NS and SL pools was 6.22 (SD = 0.92) and 6.39 (SD = 1.71), respectively. Using individual testing as reference, NS pooling of 6 had a sensitivity and specificity of 94% and 100%, respectively, with kappa of 0.97 (CI 95%: 0.93-1.00). The corresponding values for SL pooling of 6 were 83%, 100%, and 0.90 (CI 95%: 0.83-0.97). Compared with individual testing, pooling resulted in a cost reduction of 74.8% for NS and 72.4% for SL samples. Conclusions: Pooling easy-to-collect respiratory samples, especially NS, demonstrated very high diagnostic performance for detection of SARS-CoV-2 with substantial cost savings. This approach could be considered in large population screening programs, especially in LMIC.

The Role of Interface Geometry and Appendages on the Mesoscale Mechanics of the Skin.

The skin is the largest organ in the human body and serves various functions, including mechanical protection and mechanosensation. Yet, even though skin's biomechanics are attributed to two main layers - epidermis and dermis-computational models have often treated this tissue as a thin homogeneous material or, when considering multiple layers, have ignored the most prominent heterogeneities of skin seen at the mesoscale. Here we create finite element models of representative volume elements (RVEs) of skin, including the three-dimensional variation of the interface between the epidermis and dermis as well as considering the presence of hair follicles. The sinusoidal interface, which approximates the anatomical features known as Rete ridges, does not affect the homogenized mechanical response of the RVE but contributes to stress concentration, particularly at the valleys of the Rete ridges. The stress profile is three-dimensional due to the skin's anisotropy, leading to high-stress bands connecting the valleys of the Rete ridges through one type of saddle point. The peaks of the Rete ridges and the other class of saddle points of the sinusoidal surface form a second set of low-stress bands under equi-biaxial loading. Another prominent feature of the heterogeneous stress pattern is a switch in the stress jump across the interface, which becomes lower with respect to the flat interface at increasing deformations. These features are seen in both tension and shear loading. The RVE with the hair follicle showed strains concentrating at the epidermis adjacent to the hair follicle, the epithelial tissue surrounding the hair right below the epidermis, and the bulb or base region of the hair follicle. The regions of strain concentration near the hair follicle in equi-biaxial and shear loading align with the presence of distinct mechanoreceptors in the skin, except for the bulb or base region. This study highlights the importance of skin heterogeneities, particularly its potential mechanophysiological role in the sense of touch and the prevention of skin delamination.

Late autumn warming can both delay and advance spring budburst through contrasting effects on bud dormancy depth in Fagus sylvatica L.

The current state of knowledge on bud dormancy is limited. However, expanding such knowledge is crucial in order to properly model forest responses and feedback to future climate. Recent studies have shown that warming can decrease chilling accumulation and increase dormancy depth, thereby inducing delayed budburst in European beech (Fagus sylvatica L). Whether fall warming can advance spring phenology is unclear. To investigate the effect of warming on endodormancy of deciduous trees, we tested the impact of mild elevated temperature (+2.5-3.5 °C; temperature, on average, kept at 10 °C) in mid and late autumn on the bud dormancy depth and spring phenology of beech. We studied saplings by inducing periods of warming in greenhouses over a 2-year period. Even though warming reduced chilling accumulation in both years, we observed that the response of dormancy depth and spring budburst were year-specific. We found that warming during endodormancy peak could decrease the bud dormancy depth and therefore advance spring budburst. This effect appears to be modulated by factors such as the date of senescence onset and forcing intensity during endodormancy. Results from this study suggest that not only chilling but also forcing controls bud development during endodormancy and that extra forcing in autumn can offset reduced chilling.

Anisotropic damage model for collagenous tissues and its application to model fracture and needle insertion mechanics.

The analysis of tissue mechanics in biomedical applications demands nonlinear constitutive models able to capture the energy dissipation mechanisms, such as damage, that occur during tissue deformation. Furthermore, implementation of sophisticated material models in finite element models is essential to improve medical devices and diagnostic tools. Building on previous work toward microstructure-driven models of collagenous tissue, here we show a constitutive model based on fiber orientation and waviness distributions for skin that captures not only the anisotropic strain-stiffening response of this and other collagen-based tissues, but, additionally, accounts for tissue damage directly as a function of changes in the microstructure, in particular changes in the fiber waviness distribution. The implementation of this nonlinear constitutive model as a user subroutine in the popular finite element package Abaqus enables large-scale finite element simulations for biomedical applications. We showcase the performance of the model in fracture simulations during pure shear tests, as well as simulations of needle insertion into skin relevant to auto-injector design.

Dryland mechanisms could widely control ecosystem functioning in a drier and warmer world.

Responses of terrestrial ecosystems to climate change have been explored in many regions worldwide. While continued drying and warming may alter process rates and deteriorate the state and performance of ecosystems, it could also lead to more fundamental changes in the mechanisms governing ecosystem functioning. Here we argue that climate change will induce unprecedented shifts in these mechanisms in historically wetter climatic zones, towards mechanisms currently prevalent in dry regions, which we refer to as 'dryland mechanisms'. We discuss 12 dryland mechanisms affecting multiple processes of ecosystem functioning, including vegetation development, water flow, energy budget, carbon and nutrient cycling, plant production and organic matter decomposition. We then examine mostly rare examples of the operation of these mechanisms in non-dryland regions where they have been considered irrelevant at present. Current and future climate trends could force microclimatic conditions across thresholds and lead to the emergence of dryland mechanisms and their increasing control over ecosystem functioning in many biomes on Earth.

Pre-weaning performance and commercial growth curve in Dorper, Katahdin, and Romanov crossed lambs in a highland zone from central Mexico.

The aim was to evaluate the pre-weaning productive performance and growth curve of Dorper*Katahdin (DPr; n = 46), Kathadin*Kathadin (KTn; n = 204) and Romanov*Kathadin (RMv; n = 40) of commercial crossed lambs from central Mexico. We considered 1450 data from 290 crossbred lambs. The variables contemplated in this study were cross (CR), lambing type (LT), sex, birth weight (BW), weaning weight (WW), test days (TD), and daily weight gain (DWG). Correlation analysis and adjustment of growth curve were performed. Differences in CR and sex were found only in BW (p < 0.05). No differences in DWG, WW, and TD (p > 0.05) by CR and sex were found. Single lambing had the highest (p < 0.05) BW, WW, and DWG. Phenotypic correlations differ among crosses. Lambs crossed with DPr presented the highest values in parameters a and b and the lowest in c. The productive behavior of DPr, KTn, and RMv cross with KTn lambs in central Mexico is similar in the pre-weaning period; however, the growth curve and parameters that characterize it suggest that DPr lambs show a tendency to enhance productive behavior in this period.

Concordance in RT-PCR detection of SARS-CoV-2 between samples preserved in viral and bacterial transport medium.

BACKGROUND: While the detection of SARS-CoV-2 in samples preserved in viral transport medium (VTM) by RT-PCR is a standard diagnostic method, this may preclude the study of bacterial respiratory pathogens from the same specimen. It is unclear if the use of skim milk, tryptone, glucose, and glycerin (STGG) transport media, used for study of respiratory bacteria, allows an efficient and concurrent study of SARS-CoV-2 infections. OBJECTIVES: To determine the concordance in SARS-CoV-2 detection by real time RT-PCR between paired nasopharyngeal (NP) swabs preserved in STGG and nasal (NS) swabs preserved in VTM. STUDY DESIGN: Paired samples of NP and NS swabs were collected between December 2020 and March 2021 from a prospective longitudinal cohort study of 44 households and 132 participants from a peri-urban community (Lima, Peru). NP and NS swabs were taken from all participants once and twice per week, respectively, independent of respiratory symptoms. STGG medium was used for NP samples and VTM for NS samples. Samples were analyzed for SARS-CoV-2 by RT-PCR for N, S and ORF1ab targets. We calculated the concordance in detections between sample types and compared the RT-PCR cycle thresholds (Ct). RESULTS: Among the 148 paired samples, we observed a high concordance in detections between NP and NS samples (agreement = 94.59%; Kappa = 0.79). Median Ct values were statistically similar between sample types for each RT-PCR target: N, S and ORF1ab (p = 0.11, p = 0.71 and p = 0.11, respectively). CONCLUSIONS: NP swabs collected in STGG medium are reliable alternatives to nasal swabs collected in VTM for the study of SARS-CoV-2.

SARS-CoV-2 infections in households in a peri-urban community of Lima, Peru: A prospective cohort study.

BACKGROUND: We assessed the prevalence and incidence of SARS-CoV-2 infections in a prospective study of households in Lima, Peru. METHODS: Households with a child, a young adult 18-50 years, and an adult age >50 years in peri-urban Lima were followed with twice-a-week household visits during a 2-month period. Nasal swabs and saliva specimens were collected twice weekly, and nasopharyngeal swabs were collected weekly from each participant, regardless of symptoms. Laboratory-confirmed SARS-CoV-2 infection was defined by two RT-PCR tests from any of the collected specimens within a week. Blood samples collected at enrollment and end of follow-up were tested with rapid serological tests. We calculated the prevalence and incidence of laboratory-confirmed SARS-CoV-2 infections. RESULTS: We enrolled 132 participants from 44 households: 44 children, 44 young adults, and 44 older adults. A total of 13 SARS-CoV-2 infections were detected in eight households, for an overall period prevalence of 9.85% (95% confidence interval [CI]: 5.35-16.25). Most (61.54%) infections were symptomatic. Eight of 11 (72.73%) SARS-CoV-2 detections corresponded to the Lambda variant. During 218.79 person-months at risk of follow-up, there were six new SARS-CoV-2 infections detected (2.74 per 100 person-month, 95% CI: 1.25-6.04). At enrollment, 59 of 128 participants tested had positive SARS-CoV-2 IgG serology (46.09%, 95% CI: 37.25-55.12). Five of six new infections occurred among participants with negative baseline serology. CONCLUSIONS: We demonstrated high incidence of SARS-CoV-2 infections in households, especially among subjects without evidence of prior infection, most of them not detected by the Ministry of Health system.

Biaxial mechanics of thermally denaturing skin - Part 2: Modeling.

Understanding the response of skin to superphysiological temperatures is critical to the diagnosis and prognosis of thermal injuries, and to the development of temperature-based medical therapeutics. Unfortunately, this understanding has been hindered by our incomplete knowledge about the nonlinear coupling between skin temperature and its mechanics. In Part I of this study we experimentally demonstrated a complex interdependence of time, temperature, direction, and load in skin's response to superphysiological temperatures. In Part II of our study, we test two different models of skin's thermo-mechanics to explain our observations. In both models we assume that skin's response to superphysiological temperatures is governed by the denaturation of its highly collageneous microstructure. Thus, we capture skin's native mechanics via a microstructurally-motivated strain energy function which includes probability distributions for collagen fiber orientation and waviness. In the first model, we capture skin's response to superphysiological temperatures as a transition between two states that link the kinetics of collagen fiber denaturation to fiber coiling and to the transformation of each fiber's constitutive behavior from purely elastic to viscoelastic. In the second model, we capture skin's response to superphysiological temperatures instead via three states in which a sequence of two reactions link the kinetics of collagen fiber denaturation to fiber coiling, followed by a state of fiber damage. Given the success of both models in qualitatively and quantitatively capturing our observations, we expect that our work will provide guidance for future experiments that could probe each model's assumptions toward a better understanding of skin's coupled thermo-mechanics and that our work will be used to guide the engineering design of heat treatment therapies. STATEMENT OF SIGNIFICANCE: Quantifying and modeling skin thermo-mechanics is critical to our understanding of skin physiology, pathophysiology, as well as heat-based treatments. This work addresses a lack of theoretical and computational models of the coupled thermo-mechanics of skin. Our model accounts for skin microstructure through modeling the probability of fiber orientation and fiber stress-free states. Denaturing induces changes in the stress-free configuration of collagen, as well as changes in fiber stiffness and viscoelastic properties. We propose two competing models that fit all of our experimental observations. These models will enable future developments of thermal-therapeutics, prevention and management of skin thermal injuries, and set a foundation for improved mechanistic models of skin thermo-mechanics.

Drought elicits contrasting responses on the autumn dynamics of wood formation in late successional deciduous tree species.

Research on wood phenology has mainly focused on reactivation of the cambium in spring. In this study we investigated if summer drought advances cessation of wood formation and if it has any influence on wood structure in late successional forest trees of the temperate zone. The end of xylogenesis was monitored between August and November in stands of European beech and pedunculate oak in Belgium for two consecutive years, 2017 and 2018, with the latter year having experienced an exceptional summer drought. Wood formation in oak was affected by the drought, with oak trees ceasing cambial activity and wood maturation about 3 weeks earlier in 2018 compared with 2017. Beech ceased wood formation before oak, but its wood phenology did not differ between years. Furthermore, between the 2 years, no significant difference was found in ring width, percentage of mature fibers in the late season, vessel size and density. In 2018, beech did show thinner fiber walls, whereas oak showed thicker walls. In this paper, we showed that summer drought can have an important impact on late season wood phenology xylem development. This will help to better understand forest ecosystems and improve forest models.

KEYLINK: towards a more integrative soil representation for inclusion in ecosystem scale models-II: model description, implementation and testing.

New knowledge on soil structure highlights its importance for hydrology and soil organic matter (SOM) stabilization, which however remains neglected in many wide used models. We present here a new model, KEYLINK, in which soil structure is integrated with the existing concepts on SOM pools, and elements from food web models, that is, those from direct trophic interactions among soil organisms. KEYLINK is, therefore, an attempt to integrate soil functional diversity and food webs in predictions of soil carbon (C) and soil water balances. We present a selection of equations that can be used for most models as well as basic parameter intervals, for example, key pools, functional groups' biomasses and growth rates. Parameter distributions can be determined with Bayesian calibration, and here an example is presented for food web growth rate parameters for a pine forest in Belgium. We show how these added equations can improve the functioning of the model in describing known phenomena. For this, five test cases are given as simulation examples: changing the input litter quality (recalcitrance and carbon to nitrogen ratio), excluding predators, increasing pH and changing initial soil porosity. These results overall show how KEYLINK is able to simulate the known effects of these parameters and can simulate the linked effects of biopore formation, hydrology and aggregation on soil functioning. Furthermore, the results show an important trophic cascade effect of predation on the complete C cycle with repercussions on the soil structure as ecosystem engineers are predated, and on SOM turnover when predation on fungivore and bacterivore populations are reduced. In summary, KEYLINK shows how soil functional diversity and trophic organization and their role in C and water cycling in soils should be considered in order to improve our predictions on C sequestration and C emissions from soils.

KEYLINK: towards a more integrative soil representation for inclusion in ecosystem scale models. I. review and model concept.

The relatively poor simulation of the below-ground processes is a severe drawback for many ecosystem models, especially when predicting responses to climate change and management. For a meaningful estimation of ecosystem production and the cycling of water, energy, nutrients and carbon, the integration of soil processes and the exchanges at the surface is crucial. It is increasingly recognized that soil biota play an important role in soil organic carbon and nutrient cycling, shaping soil structure and hydrological properties through their activity, and in water and nutrient uptake by plants through mycorrhizal processes. In this article, we review the main soil biological actors (microbiota, fauna and roots) and their effects on soil functioning. We review to what extent they have been included in soil models and propose which of them could be included in ecosystem models. We show that the model representation of the soil food web, the impact of soil ecosystem engineers on soil structure and the related effects on hydrology and soil organic matter (SOM) stabilization are key issues in improving ecosystem-scale soil representation in models. Finally, we describe a new core model concept (KEYLINK) that integrates insights from SOM models, structural models and food web models to simulate the living soil at an ecosystem scale.

Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters.

OBJECTIVE: Leucine was previously demonstrated to allosterically activate mammalian sirtuin 1 and synergize with other sirtuin 1/AMP-activated protein kinase/nitric oxide pathway activators to modulate energy metabolism. The objective of this study was to evaluate the effects of a triple combination of leucine, metformin, and sildenafil (NS-0200) on body weight and obesity comorbidities in a phase 2 randomized trial. METHODS: A total of 91 subjects with obesity were randomized to placebo, low dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil), or high dose (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) twice daily for 16 weeks. Seventy subjects completed the trial and met all a priori compliance criteria. Hypertensive (n = 35) and hypertriglyceridemic (n = 22) subcohorts were also analyzed. RESULTS: NS-0200 dose-responsively reduced weight; high dose reduced weight by 2.4 and 5.0 kg in the full and high-triglyceride cohorts, respectively (P < 0.0001). High-dose NS-0200 treatment also decreased blood pressure (-5.5 mm Hg diastolic pressure; P = 0.011), with greater effects among hypertensive subjects. NS-0200 also significantly reduced triglycerides and hemoglobin A1c. Significant improvement in ≥ 2 comorbidities was exhibited by 54% of subjects in the high-dose arm versus 5% of placebo subjects (P = 0.0009). Treatment-emergent adverse events did not significantly differ among groups. CONCLUSIONS: These data support further study of NS-0200 as a therapy for obesity and associated comorbidities.

Spatial patterns of species richness and nestedness in ant assemblages along an elevational gradient in a Mediterranean mountain range.

BACKGROUND: The study of biodiversity spatial patterns along ecological gradients can serve to elucidate factors shaping biological community structure and predict ecosystem responses to global change. Ant assemblages are particularly interesting as study cases, because ant species play a key role in many ecosystem processes and have frequently been identified as useful bioindicators. METHODS: Here we analyzed the response of ant species richness and assemblage composition across elevational gradients in Mediterranean grasslands and subsequently tested whether these responses were stable spatially and temporally. We sampled ant assemblages in two years (2014, 2015) in two mountain ranges (Guadarrama, Serrota) in Central Spain, along an elevational gradient ranging from 685 to 2390 m a.s.l. RESULTS: Jackknife estimates of ant species richness ranged from three to 18.5 species and exhibited a hump-shaped relationship with elevation that peaked at mid-range values (1100-1400 m). This pattern was transferable temporally and spatially. Elevation was related to ant assemblage composition and facilitated separation of higher elevation assemblages (> 1700 m) from the remaining lower elevation species groups. Ant assemblages were nested; therefore species assemblages with a decreased number of species were a subset of the richer assemblages, although species turnover was more important than pure nestedness in all surveys. The degree of nestedness changed non-linearly as a cubic polynomial with elevation. These assembly patterns coincided more clearly over time than between the two study regions. DISCUSSION: We suggest double environmental stressors typical of Mediterranean mountains explained species richness patterns: drought at low elevations and cold temperatures at high elevations likely constrained richness at both extremes of elevational gradients. The fact that species turnover showed a dominant role over pure nestedness suggested current ant assemblages were context-dependent and highly vulnerable to global change, which threatens the conservation of present day native ant communities, particularly at high elevations.

Association Between Magnetic Resonance Imaging-Proton Density Fat Fraction and Liver Histology Features in Patients With Nonalcoholic Fatty Liver Disease or Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) often require histologic assessment via liver biopsy. Magnetic resonance imaging (MRI)-based methods for measuring liver triglycerides based on proton density fat fraction (PDFF) are increasingly used as a noninvasive tool to identify patients with hepatic steatosis and to assess for change in liver fat over time. We aimed to determine whether MRI-PDFF accurately reflects a variety of liver histology features in patients with NAFLD or NASH. METHODS: We performed a retrospective analysis of pooled data from 3 phase 2a trials of pharmacotherapies for NAFLD or NASH. We collected baseline clinical, laboratory, and histopathology data on all subjects who had undergone MRI analysis in 1 of the trials. We assessed the relationship between liver PDFF values and liver histologic findings using correlation and area under the receiver operating characteristic (AUROC) analyses. As an ancillary analysis, we also simulated a clinical trial selection process and calculated subject exclusion rates and differences in population characteristics caused by PDFF inclusion thresholds of 6% to 15%. RESULTS: In 370 subjects, the mean baseline PDFF was 17.4% ± 8.6%. Baseline PDFF values correlated with several histopathology parameters, including steatosis grade (r = 0.78; P < .001), NAFLD activity score (NAS, r = 0.54; P < .001), and fibrosis stage (r = -0.59; P < .001). However, PDFF did not accurately identify patients with NAS ≥ 4 (AUROC = 0.72) or fibrosis stage ≥3 (AUROC = 0.66). In a theoretical trial of these subjects, exclusion rates increased as PDFF minimum threshold level increased. There were no significant differences in cohort demographics when PDFF thresholds ranging from 6% to 15% were used, and differences in laboratory and histopathology data were small. CONCLUSIONS: In an analysis of patients with NAFLD or NASH, we determined that although The MRI-PDFF correlated with steatosis grade and NAS, and inversely with fibrosis stage, it was suboptimal in identification of patients with NAS >4 or advanced fibrosis. Although MRI-PDFF is an important imaging biomarker for continued evaluation of this patient population, liver biopsy analysis is still necessary.

Replication of many human viruses is refractory to inhibition by endogenous cellular microRNAs.

The issue of whether viruses are subject to restriction by endogenous microRNAs (miRNAs) and/or by virus-induced small interfering RNAs (siRNAs) in infected human somatic cells has been controversial. Here, we address this question in two ways. First, using deep sequencing, we demonstrate that infection of human cells by the RNA virus dengue virus (DENV) or West Nile virus (WNV) does not result in the production of any virus-derived siRNAs or viral miRNAs. Second, to more globally assess the potential of small regulatory RNAs to inhibit virus replication, we used gene editing to derive human cell lines that lack a functional Dicer enzyme and that therefore are unable to produce miRNAs or siRNAs. Infection of these cells with a wide range of viruses, including DENV, WNV, yellow fever virus, Sindbis virus, Venezuelan equine encephalitis virus, measles virus, influenza A virus, reovirus, vesicular stomatitis virus, human immunodeficiency virus type 1, or herpes simplex virus 1 (HSV-1), failed to reveal any enhancement in the replication of any of these viruses, although HSV-1, which encodes at least eight Dicer-dependent viral miRNAs, did replicate somewhat more slowly in the absence of Dicer. We conclude that most, and perhaps all, human viruses have evolved to be resistant to inhibition by endogenous human miRNAs during productive replication and that dependence on a cellular miRNA, as seen with hepatitis C virus, is rare. How viruses have evolved to avoid inhibition by endogenous cellular miRNAs, which are generally highly conserved during metazoan evolution, remains to be determined. Importance: Eukaryotic cells express a wide range of small regulatory RNAs, including miRNAs, that have the potential to inhibit the expression of mRNAs that show sequence complementarity. Indeed, previous work has suggested that endogenous miRNAs have the potential to inhibit viral gene expression and replication. Here, we demonstrate that the replication of a wide range of pathogenic viruses is not enhanced in human cells engineered to be unable to produce miRNAs, indicating that viruses have evolved to be resistant to inhibition by miRNAs. This result is important, as it implies that manipulation of miRNA levels is not likely to prove useful in inhibiting virus replication. It also focuses attention on the question of how viruses have evolved to resist inhibition by miRNAs and whether virus mutants that have lost this resistance might prove useful, for example, in the development of attenuated virus vaccines.

A neuron-specific host microRNA targets herpes simplex virus-1 ICP0 expression and promotes latency.

After infecting peripheral sites, herpes simplex virus (HSV) invades the nervous system and initiates latent infection in sensory neurons. Establishment and maintenance of HSV latency require host survival, and entail repression of productive cycle ("lytic") viral gene expression. We find that a neuron-specific microRNA, miR-138, represses expression of ICP0, a viral transactivator of lytic gene expression. A mutant HSV-1 (M138) with disrupted miR-138 target sites in ICP0 mRNA exhibits enhanced expression of ICP0 and other lytic proteins in infected neuronal cells in culture. Following corneal inoculation, M138-infected mice have higher levels of ICP0 and lytic transcripts in trigeminal ganglia during establishment of latency, and exhibit increased mortality and encephalitis symptoms. After full establishment of latency, the fraction of trigeminal ganglia harboring detectable lytic transcripts is greater in M138-infected mice. Thus, miR-138 is a neuronal factor that represses HSV-1 lytic gene expression, promoting host survival and viral latency.