Small Alterations Research Articles

Phenotypes linked to duplication upstream of SOX9: New insights into presentation and diagnosis.

Duplications occurring upstream of the SOX9 gene have been identified in a limited subset of patients with 46,XX testicular/ovotesticular differences/disorders of sex development (DSD). However, comprehensive understanding regarding their clinical presentation and diagnosis is limited. To gain further insight into the diagnosis of a large cohort of 46,XX individuals with duplications upstream of SOX9. We retrospectively analyzed data of 46,XX/SRY-negative individuals with SOX9 upstream duplications. Clinical data were recorded, and genetic etiologies were investigated using karyotyping, fluorescence in situ hybridization (FISH) for SRY analysis, microarray analysis, multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing panels including whole genome sequencing. We analyzed twelve 46,XX individuals with heterozygous duplications upstream of SOX9, ranging from 107-941 kb. Ages at diagnosis ranged from 0.1 to 55 years. Seven (58%) had testicular/ovotesticular DSD, while five (41%) were asymptomatic carriers detected through family screening. There was no significant correlation between duplication size and genital/gonadal phenotype. The duplication was inherited from the father (n=3) or an asymptomatic mother (n=2). In one family, a duplication missed by the 300K microarray was detected by MLPA and confirmed with the 750K microarray. 46,XX individuals with SOX9 upstream duplications may exhibit no symptoms, but thorough family screening is crucial due to the potential inheritance and testicular/ovotesticular DSD risk in subsequent generations. We emphasize the effectiveness of high-resolution microarray analysis (>500K) as the primary diagnostic tool for 46,XX/SRY-negative testicular/ovotesticular DSD individuals, enabling thorough genome-wide assessment of copy number variations and detecting small alterations.

Shedding new light on quadrupolar 1,4-dihydropyrrolo[3,2-b]pyrroles: impact of electron-deficient scaffolds over emission.

In this work, we disclose a series of seven quadrupolar centrosymmetric 1,4-dihydropyrrolo[3,2-b]pyrroles (DHPPs) linked to the two peripheral, strongly electron-accepting heterocycles such as benzoxadiazole, benzothiadiazole and benzoselenadiazole. This represents the first study probing the influence of electron-deficient heterocycles, rather that small electron-withdrawing substituents, on photophysics of DHPPs. These new acceptor-donor-acceptor hybrid dyes exhibit an appreciable combination of photophysical properties including absorption maxima in the range of 470-620 nm, and emission in the range of 500-720 nm with fluorescence quantum yields reaching 0.88. We discovered that the presence of two 7-nitro-benzoxadiazolyl substituents at positions 2 and 5 of DHPP core, evokes a strong fluorescence in non-polar solvents shifted to 639 nm. This is the most bathochromically shifted emission for quadrupolar, centrosymmetric chromophore bearing exclusively biaryl linkages. Interestingly, 1,2,4,5-tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole (TAPP) possessing 4-benzothiadiazolyl groups is strongly emitting in the crystalline state (fluorescence quantum yield = 0.43). The combined photophysical and crystallographic studies point towards existence of intermolecular hydrogen bonds which modify the dihedral angles between the donor and acceptor moieties as a primary reason for this strong emission. Small structural alteration via the replacement of two 2,1,3-benzoxadiazole scaffolds with 2,1,3-benzoxadiazole-2-oxide moieties causes >103 decrease in the fluorescence intensity. Computational studies point out to strong charge transfer originating from exceptionally large dihedral angles as the pivotal reason of this phenomenon. Although internal conversion originating from the charge-transfer state is the prevailing non-radiative deactivation mechanism, intersystem crossing also plays a role. The rational design of DHPPs that enables modulation of emission will advance their applicability.

Chromosomal rearrangements and instability caused by the LINE-1 retrotransposon.

LINE-1 (L1) retrotransposition is widespread in many cancers, especially those with a high burden of chromosomal rearrangements. However, whether and to what degree L1 activity directly impacts genome integrity is unclear. Here, we apply whole-genome sequencing to experimental models of L1 expression to comprehensively define the spectrum of genomic changes caused by L1. We provide definitive evidence that L1 expression frequently and directly causes both local and long-range chromosomal rearrangements, small and large segmental copy-number alterations, and subclonal copy-number heterogeneity due to ongoing chromosomal instability. Mechanistically, all these alterations arise from DNA double-strand breaks (DSBs) generated by L1-encoded ORF2p. The processing of ORF2p-generated DSB ends prior to their ligation can produce diverse rearrangements of the target sequences. Ligation between DSB ends generated at distal loci can generate either stable chromosomes or unstable dicentric, acentric, or ring chromosomes that undergo subsequent evolution through breakage-fusion bridge cycles or DNA fragmentation. Together, these findings suggest L1 is a potent mutagenic force capable of driving genome evolution beyond simple insertions.

Cluster sets lead to better performance maintenance and minimize training-induced fatigue than traditional sets

ObjectiveThe aim of this study was to examine the acute effects on mechanical, neuromuscular, metabolic, and muscle contractile responses to different set configurations in full-squat (SQ).MethodsTwenty-two men performed three SQ sessions that consisted of 3 sets of 12 repetitions with 60% 1RM with 4 minutes inter-set rests: a) traditional set (TS): no rest within the set; b) cluster-6 (CS6): a 30 seconds intraset rest after the 6th repetition of each set; and c) cluster-2 (CS2): a 30 seconds intraset rest every 2 repetitions. Mechanical (i.e., force, velocity, and power) and electromyography (EMG) values were recorded for every repetition. A battery of tests was performed: a) tensiomyography (TMG), b) blood lactate c), countermovement jump (CMJ), d) maximal isometric SQ, and e) performance with the load that resulted in a velocity of 1 m·s−1 at baseline (V1-load). Repeated measured ANOVA analyses were used to compare the 3 protocols.ResultsAs the number of intraset rests increased (TS < CS6 < CS2), mechanical performance was better maintained (p < 0.01) and EMG variables were less altered (p = 0.05). At post, CS2 and CS6 displayed lower lactate concentration, lesser reductions in CMJ height, and smaller alterations in TMG-derived variables than TS (p < 0.05).ConclusionThe introduction of short and frequent intraset rest periods during resistance exercise alleviates training-induced fatigue, resulting in better maintenance of performance. This approach can be applied during the in-season period when minimizing fatigue is a priority.

Genomic Proximity Mapping (GPM): Evaluation of a Next Generation Cytogenomic Assay for Improved Risk Stratification in Acute Myeloid Leukemia

Cytogenetics encompasses a suite of diagnostics assays that provides critical diagnostic and prognostic information that can help guide care for acute myeloid leukemias (AML) patients. Routine cytogenetic workup for AML includes karyotyping and fluorescence in situ hybridization (FISH) for known recurrent variants. The workup can be extended to include chromosome genome array testing (CGAT) but because all 3 of these tests have a non-overlapping set of limitations that can necessitate multiple, often iterative, rounds of testing in complex cases and may miss information in cases with cryptic fusions or small copy number alterations. Therefore, there is an unmet need for an accurate, fast and reliable test that can provide a solution to these limitations. In this study, we evaluate Genomic Proximity Mapping (GPM), a novel method that captures much of the same information as karyotyping, FISH, and CGAT in a single assay. GPM uses proximity ligation sequencing to capture ultra-long range contiguity information from conventional short-read sequencing. In brief, 200,000-500,000 cells from bone marrow, peripheral blood, or aphersis samples are crosslinked with formalin prior to library preparation. Because sequences that are closer on a chromosome are more likely to physically interact and be crosslinked, GPM can use the frequency pairwise of crosslinked sequence interactions to determine the structure of chromosomes. In order to evaluate its performance, we benchmarked GPM against standard-of-care cytogenetics conducted on newly diagnosed 166 AML cases in a multicenter, retrospective study utilizing real-world patient samples. There was a strong concordance between GPM and cytogenetic findings, with 100% of European LeukemiaNet (ELN) specified cytogenetic risk variants identified by cytogenetic being identified by GPM. However, GPM also identified additional variants of known clinical significance not observed by standard-of-care cytogenetics. To determine if GPM findings had clinical benefits for risk stratification, we compared overall survival (OS) of patients, risk-stratified using ELN 2022 criteria, using either cytogenetics or GPM to determine the cytogenetic abnormalities. Separation of favorable, intermediate, and adverse risk categories were statistically significant when variants identified either by cytogenetics or GPM were used for risk categorization (GPM, P = 0.0006; cytogenetics P = 0.0009 for GPM and cytogenetics, Mantel-Cox log rank test). However, Kaplan-Meier analysis demonstrated that GPM greater separation in intermediate (median OS 2.1 years for GPM and 2.4 years for cyto), and adverse (median OS 1.1 yrs for GPM and 0.9 years for cytogenetics) categories. The ELN-directed risk based on karyotype and FISH presentation was revised for 14 (8.4%) out of 166 cases with available data based on GPM assay results. These findings argue that GPM can be used as a single assay to accurately stratify AML patient risk and may provide additional benefits over cytogenetics, yielding more accurate risk stratification. Support: NIH/NCI U10CA180888, U10CA180819, U24CA196175, R44CA278140

Neurodevelopmental Process Monitoring of Cytosine Arabinoside-Exposed Neurons Using Raman Spectroscopy.

Raman spectroscopy is used to monitor the development of live neurons exposed to cytosine arabinoside (ara-C). Ara-C is widely used to culture neurons and exclude non-neuronal cells. In this study, Raman spectra obtained from neurons exposed to ara-C were plotted using an analytical model of neuronal development to evaluate the impact of ara-C on neuronal development. After two days of culturing, neurons were exposed to ara-C for 24 h at final concentrations of 0 (control), 5, and 25 μM. Principal component analysis (PCA) was performed to build an analytical model for evaluating neurodevelopmental disorders caused by ara-C treatment. We projected the Raman spectra obtained from ara-C-treated cells onto the control group dataset. The distribution of PC1 scores for neurons exposed to ara-C at a final concentration of 5 μM was not significantly different from that of the control group. In contrast, under a final concentration of 25 μM, the data population at 10 and 15 days of culturing overlapped significantly with that of neurons at 4 days of normal culturing. These results suggest that Raman spectroscopy can detect very small physiological alterations in the neurons even after a short-term exposure (24 h) of ara-C. Our analytical method has high potential to evaluate the developmental stages for living neurons under exposure to chemicals.

Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases

When used to edit genomes, Cas9 nucleases produce targeted double-strand breaks in DNA. Subsequent DNA-repair pathways can induce large genomic deletions (larger than 100 bp), which constrains the applicability of genome editing. Here we show that Cas9-mediated double-strand breaks induce large deletions at varying frequencies in cancer cell lines, human embryonic stem cells and human primary T cells, and that most deletions are produced by two repair pathways: end resection and DNA-polymerase theta-mediated end joining. These findings required the optimization of long-range amplicon sequencing, the development of a k-mer alignment algorithm for the simultaneous analysis of large DNA deletions and small DNA alterations, and the use of CRISPR-interference screening. Despite leveraging mutated Cas9 nickases that produce single-strand breaks, base editors and prime editors also generated large deletions, yet at approximately 20-fold lower frequency than Cas9. We provide strategies for the mitigation of such deletions.

Mutations Selectively Evolving Peroxidase Activity Among Alternative Catalytic Functions of Human Glutathione Transferase P1-1.

Glutathione transferases are detoxication enzymes with broad catalytic diversity, and small alterations to the protein's primary structure can have considerable effects on the enzyme's substrate selectivity profile. We demonstrate that two point mutations in glutathione transferase P1-1 suffice to generate 20-fold enhanced non-selenium-dependent peroxidase activity indicating a facile evolutionary trajectory. Designed mutant libraries of the enzyme were screened for catalytic activities with alternative substrates representing four divergent chemistries. The chemical reactions comprised aromatic substitution, Michael addition, thiocarbamoylation, and hydroperoxide reduction. Two mutants, R1 (Y109H) and an R1-based mutant V2 (Q40M-E41Q-A46S-Y109H-V200L), were discovered with 16.3- and 30-foldincreased peroxidase activity with cumene hydroperoxide (CuOOH) compared to the wildtype enzyme, respectively. The basis of the improved peroxidase activity of the mutant V2 was elucidated by constructing double-point mutants. The mutants V501 (Q40M-Y109H) and V503 (E41Q-Y109H) were found to have 20- and 21-fold improvements in peroxidase activity relative to the wildtype enzyme, respectively. The steady-state kinetic profiles of mutants R1 and V2 in the reduction of CuOOH were compared to the wildtype parameters. The kcat values for R1 and V2 were 34- and 57-fold higher, respectively, than that of the wildtype enzyme, whereas the mutant Km values were increased approximately 3-fold. A 10-fold increased catalytic efficiency (kcat/Km) in CuOOH reduction is accomplished by the Tyr109His point mutation in R1. The 23-fold increase of the efficiency obtained in V2 was caused by adding further mutations primarily enhancing kcat. In all mutants with elevated peroxidase activity, His109 played a pivotal role.

Mitochondrial small RNA alterations associated with increased lysosome activity in an Alzheimer's Disease Mouse Model uncovered by PANDORA-seq.

Emerging small noncoding RNAs (sncRNAs), including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), are critical in various biological processes, such as neurological diseases. Traditional sncRNA-sequencing (seq) protocols often miss these sncRNAs due to their modifications, such as internal and terminal modifications, that can interfere with sequencing. We recently developed panoramic RNA display by overcoming RNA modification aborted sequencing (PANDORA-seq), a method enabling comprehensive detection of modified sncRNAs by overcoming the RNA modifications. Using PANDORA-seq, we revealed a novel sncRNA profile enriched by tsRNAs/rsRNAs in the mouse prefrontal cortex and found a significant downregulation of mitochondrial tsRNAs and rsRNAs in an Alzheimer's disease (AD) mouse model compared to wild-type controls, while this pattern is not present in the genomic tsRNAs and rsRNAs. Moreover, our integrated analysis of gene expression and sncRNA profiles reveals that those downregulated mitochondrial sncRNAs negatively correlate with enhanced lysosomal activity, suggesting a crucial interplay between mitochondrial RNA dynamics and lysosomal function in AD. Given the versatile tsRNA/tsRNA molecular actions in cellular regulation, our data provide insights for future mechanistic study of AD with potential therapeutic strategies.

Functional Upper Limb Assessment After Sternal Clavicular Joint Resection Without Prosthetic Reconstruction

The Sternal Clavicular Joint (SCJ) resection is used as a treatment for SCJ infections. Reconstruction with a prosthesis can lead to reinfection, but theoretically, it is preferable due to functional impairment risk. However, the post-operative functional upper limb evaluation is poorly documented. The objective is to assess the upper limb function after SCJ resection and reconstruction without a prosthesis to determine if there is any functional impact and to grade it. We performed clinical and functional evaluations of patients with SCJ resected and reconstructed without prosthesis as treatment of SCJ infection in the period between 2012-2018. The evaluation was composed of a questionnaire (pain scale and daily activity evaluation) and examination (inspection, mobility and strength). 9 patients were assessed, from whom 7 had unilateral surgery. The questionnaires regarding pain and daily activities limitations showed improvement in 100% of the cases. Just one case of possible nerve injury with paresthesia. On the physical exam, only small alterations on inspection were found in 8 patients. Mobility was considered normal in 33%, partially impaired in one test in 22% and partially impaired in two or more tests in 44% of cases. Strength was graded 5 (maximum strength) and symmetric in seven patients. Patients after SCJ resection without prosthetic reconstruction showed a good outcome, especially on pain and daily activity. Even though, a small impact in mobility and strength has occurred.

Incorporation of ESIPT into pillar[5]arene for solid-state dual emission responsive to n-hexane vapor

Abstract Pillar[5]arene is a promising macrocyclic receptor of a chemical sensor showing shape-selective encapsulation of neutral molecules into the cavity, but the poor fluorescence properties remain a challenge. Herein, we report a pillar[5]arene coupled with 2-(2-hydroxyphenyl)benzoxazole (HBO), which displays bright fluorescence in both solution and the solid state. Owing to the excited-state intramolecular proton transfer (ESIPT) in the HBO moiety, greatly improved fluorescence is observed for the pillar[5]arene derivative in CHCl3 (Φlum = 11%) and powder form (Φlum = 25%). Moreover, the emission color changes from light green to blue when the powder sample is exposed to n-hexane vapor. The color change derives from variable dual emission via ESIPT and excimer-forming pathways, as suggested by fluorescence lifetime measurements at different wavelengths. Powder x-ray diffraction indicates that increased crystallinity and a small alteration in the solid-state structure leads to visible fluorescent chromism upon vapor encapsulation.

Age-dependencies of the electroretinogram in healthy subjects.

The purpose of this study was to evaluate the age-dependency of amplitudes and implicit times in the electroretinograms (ERGs) of healthy individuals and provide clinicians and researchers with a reference for a variety of stimulus paradigms. Full-field electroretinography was conducted on 73 healthy participants aged 14-73 using an extended ISCEV standard protocol that included an additional 9Hz flicker stimulus for assessing rod function and special paradigms for isolated On-Off and S-cone responses. Correlation coefficients and best-fit regression models for each parameter's age-dependency were calculated. Dark-adapted ERGs, in particular, displayed notable age-related alterations. The attenuation and delay of the b-wave with higher age were most significant in the dark-adapted, rod-driven 0.001cds/m2 flash ERG. The age-dependent reduction of the a-wave amplitude was strongest in the standard dark-adapted 3cds/m2 flash condition. Cone-driven, light-adapted responses to either flash or flicker stimuli displayed comparatively small alterations at higher age. S-cone function tended to diminish at an early age, but the effect was not significant in the whole population. The results suggest that rod and cone function decline at different rates with age, with rods being generally more affected by aging. Nonetheless, response amplitudes displayed a wide variability across the whole sample.

Less Pain, but no changes in maximal inclination angles during an overhead reach task following local anesthetic in patients with ongoing shoulder pain

This multicenter observational study aimed to assess how pain reduction, induced by local anesthesia, affects the relative angular contributions of the shoulder girdle and trunk to the maximal angular performance during a semi-constrained overhead reach task in patients with ongoing shoulder pain. Twenty-nine individuals (age 59.0 SD 12.8 years;16-male) with symptomatic shoulders were administered corticosteroid and lidocaine injections by their attending orthopedic surgeon. Immediately before and after the injections, participants reached for a target on the ceiling ten times as high as possible while their pain levels, shoulder, and trunk movements were recorded. The analysis revealed that there was a significant reduction in pain following the injections. However, there were no significant differences in maximum shoulder and trunk inclination angles between the pre- and post-injection conditions. Notably, there were slight but statistically significant alterations in humeroscapular kinematics during the initial phase of arm elevation following the injections. In conclusion, acute pain relief following local anesthetics is not associated with immediate alterations in maximum shoulder girdle and trunk inclination angles during a semi-constrained overhead reach task in patients with ongoing shoulder pain. However, there are signs of small alterations in humeroscapular kinematics during the initial phase of arm elevation.

Thirty Years of Hide-and-Seek: Capturing Abundant but Elusive MIII@C3v(8)-C82 Isomer, and the Study of Magnetic Anisotropy Induced in Dy3+ Ion by the Fullerene π-Ligand.

Our knowledge about endohedral metallofullerenes (EMFs) is restricted to the structures with sufficient kinetic stability to be extracted from the arc-discharge soot and processed by chromatographic and structural techniques. For the most abundant rare-earth monometallofullerene MIII@C82, experimental studies repeatedly demonstrated C2v(9) and Cs(6) carbon cage isomers, while computations predicted equal stability of the "missing" C3v(8) isomer. Here we report that this isomer is indeed formed but has not been recovered from soot using standard protocols. Using a combination of redox extraction and subsequent benzylation and trifluoromethylation with single-crystal XRD analysis of CF3 adduct, we prove that Dy@C3v(8)-C82 is one of the most abundantly produced metallofullerenes, which was not identified in earlier studies because of the low kinetic stability. Further, using the Dy@C3v(8)-C82(CF3) and Dy@C3v(8)-C82(CH2Ph) monoadducts for the case study, we analyzed the role of metal-fullerene bonding on the single-ion magnetic anisotropy of Dy in EMFs. The multitechnique approach, combining ab initio calculations, EPR spectroscopy, and SQUID magnetometry, demonstrated that coordination of the Dy ion to the fullerene cage induces moderate, nonaxial, and very fluid magnetic anisotropy, which strongly varies with small alterations in the Dy-fullerene coordination geometry. As a result, Dy@C3v(8)-C82(CH2Ph) is a weak field-induced single-molecule magnet (SMM), whose signatures of magnetic relaxation are detectable only below 3 K. Our results demonstrate that metal-cage interactions should have a detrimental effect on the SMM performance of EMFs. At the same time, the strong variability of the magnetic anisotropy with metal position suggests tunability and offers strategies for future progress.

Thrombosis and Thrombotic Risk in Athletes.

The hemostatic system is characterized by a delicate balance between pro- and anticoagulant forces, and the smallest alteration can cause serious events such as hemorrhages or thrombosis. Although exercise has been shown to play a protective role in athletes, several factors may increase the risk of developing venous thromboembolism (VTE), including hemoconcentration induced by exertion, immobilization following sports injuries, frequent long-distance flights, dehydration, and the use of oral contraceptives in female athletes. Biomarkers such as D-dimer, Factor VIII, thrombin generation, inflammatory cytokines, and leukocyte count are involved in the diagnosis of deep vein thrombosis (DVT), although their interpretation is complex and may indicate the presence of other conditions such as infections, inflammation, and heart disease. Therefore, the identification of biomarkers with high sensitivity and specificity is needed for the screening and early diagnosis of thromboembolism. Recent evidence about the correlation between the intensity of physical activity and VTE is divergent, whereas the repeated gestures in sports such as baseball, hockey, volleyball, swimming, wrestling, or, on the other hand, soccer players, runners, and martial art training represent a risk factor predisposing to the onset of upper and lower DVT. Anticoagulant therapy is the gold standard, reducing the risk of serious complications such as pulmonary embolism. The aim of this review is to provide a general overview about the interplay between physical exercise and the risk of thromboembolism in athletes, focusing on the main causes of thrombosis in professional athletes and underlying the need to identify new markers and therapies that can represent a valid tool for safeguarding the athlete's health.

Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort.

Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Previous genomic evidence identified four ACs potentially linked to depression risk. We carried forward these ACs and tested the association of their circulating levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles. The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1035) or remitted (n = 739) MDD and healthy controls (n = 800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology. As compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen's d = 0.2, p ≤ 1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß=0.06, SE = 0.02, p = 1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß=-0.05, SE = 0.02, p = 1.85e-2) and higher C3 (ß=0.08, SE = 0.02, p = 3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4141 observations). Small alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.

Redistribution of fine gold from hydrothermal sources to sedimentary sinks, Rakaia River, Canterbury, New Zealand

ABSTRACT The Rakaia River in the South Island of New Zealand is a unique catchment in which to trace active detrital gold transport, deformation and concentration from near-coeval orogenic sources. The catchment hosts widespread small late Cenozoic hydrothermal alteration zones, some of which are gold-bearing, in actively rising and eroding mountain headwaters. Detrital gold liberated from the sources is distinctively porous with abundant micron-scale silicate inclusions, especially albite. Fine gold (∼200–100 µm) has been transported >100 km downstream, but coarse gold remains highly diluted in proximal fluvial sediments. Fine gold is also diluted by coarse fluvial sediments that form the upper kilometre of the Canterbury sedimentary basin southeast of the mountain front. Minor re-concentration of fine gold occurs in a bedrock gorge at the mountain front, and on steep ocean beaches beyond the river mouth. Despite the long-distance transport, the fine gold particles have been only superficially modified by surface smearing and minor flattening. The gold may have travelled in suspension in the river, buoyed by electrostatically adhering fine micas, in contrast to detrital garnets that were rounded in bed-load. In contrast, detrital gold on the western side of the mountains has been flattened to thin flakes during bed-load transport.

Lifshitz Transition in a Single-Atom-Thick GdxYb1-xPb3 Kagome Compound on Si(111).

Lanthanide (Ln) elements Gd and Yb alloyed with a Pb monolayer on the Si(111) substrate form LnPb3 compounds having the same crystal structure. They comprise a single-atom-thick Pb layer arranged in a slightly distorted kagome lattice with Ln atoms filling the hexagonal voids. They have similar electronic band structures except for the Fermi level position, which varies between the divalent Yb- and trivalent Gd-containing compounds by ∼0.47 eV. The ability to create a 2D solid solution with the unified continuous Pb layer and hexagonal voids randomly filled with either Gd or Yb atoms allows precise control of the Fermi level position. Small alteration of the Fermi level triggers drastic changes in the Fermi surface topology due to the Lifshitz transition, hence in the physical properties. In particular, the sheet resistance of the GdxYb1-xPb3/Si(111) system can be controllably varied over an order of magnitude range.

Assessing background levels of trace elements in soils of Mato Grosso (Brazil) for environmental and food security

The State of Mato Grosso, Brazil, presents a great diversity of soils and landscapes, and many areas of agriculture and mining. However, the natural content of trace elements in the soil are still little known, which represents a great gap for studies and/or regulations concerning soil and food security. This study proposes to establishing quality reference values ​​(QRVs) for trace elements in Mato Grosso soils. Soil sampling was carried out to cover the geodiversity of soils in this region, considering geology, geomorphology, lithology, pedology and biomes, in addition to summarizing the data available in the literature to form the database for this study. The soil was analyzed for the contents of Fe, Mn, Cu, Zn, Ni, Cr, Ba, Pb, As, Cd and Hg, according to the USEPA 3051A methodology. Trace element results based on soil geodiversity contributed to a general description of how levels of these elements may be related to the environmental factors studied. The levels of main elements related to the environmental factors were Mn and Zn to geology; Mn, Cr, Ba, Zn, As and Cd to geomorphology; Mn to lithology; Mn and Cr to pedology; and Mn, As, Cd and Hg to the biome. It was not possible to propose QRVs grouped by environmental factors for the State of Mato Grosso, especially due to the large territorial extension covered. Thus, the QRVs were proposed in the 90th percentile, in mg kg−1, as follows: Fe 23,128; Mn 351; Cu 16.50; Zn 29.24; Ni 8.86; Cr 52.73; Ba 84.45; Pb 13.42; As 7.60; Cd 0.87; and Hg 0.10. Mercury, Cd, and As levels require careful regional monitoring, as some environments, such as the Amazon biome, may present naturally high levels, and small alterations in the bioavailability of such elements might represent a risk to health or the environment.

Structure-function in smokers: when a small airways test really reflects the small airways.

If multiple-breath washout (MBW)-derived acinar ventilation heterogeneity (Sacin) really represents peripheral units, the N2 phase-III of the first MBW exhalation should be curvilinear. This is essentially due to the superposed effect of gas diffusion and convection resulting in an equilibration of N2 concentrations between neighboring lung units throughout exhalation. We investigated this in smokers with computed tomography (CT)-proven functional small airway disease. Instantaneous N2-slopes were computed over 40-ms intervals throughout phase-III and normalized by mean phase-III N2 concentration. N2 phase-III (concave) curvilinearity was quantified as the rate at which the instantaneous N2-slope decreases past the phase-II peak over a 1-s interval; for a linear N2 phase-III unaffected by diffusion, this rate would amount to 0 L-1/s. N2 phase-III curvilinearity was obtained on the experimental curves and on existing model simulations of N2 curves from a normal peripheral lung model and one with missing terminal bronchioles (either 50% or 30% TB left). In 46 smokers [66 (±8) yr; 49 (±26) pack·yr] with CT-based evidence of peripheral lung destruction, instantaneous N2-slope decrease was compared between those with (fSAD+fEmphys) > 20% [-0.26 ± 0.14 (SD) L-1/s; n = 24] and those with (fSAD+fEmphys) < 20% [-0.16 ± 0.12 (SD) L-1/s; n = 22] (P = 0.014). Experimental values fell in the range predicted by a realistic peripheral lung model with progressive reduction of terminal bronchioles: values of instantaneous N2-slope decrease obtained from model simulations were -0.09 L-1/s (normal lung; 100% TB left), -0.17 L-1/s (normal lung 50% TB left), and -0.29 L-1/s (30% TB left). In smokers with CT-based evidence of functional small airway alterations, it is possible to demonstrate that Sacin really does represent the most peripheral airspaces.NEW & NOTEWORTHY In smokers with computed tomography-based evidence of functional small airway alterations by parametric response mapping, it is possible to demonstrate that the multiple-breath washout-derived Sacin, an index of acinar ventilation heterogeneity, actually does represent the most peripheral airspaces. This is done by verifying on experimental N2 washout curves of the first breath, N2 phase-III concavity predicted by the diffusion-convection interdependence model.