Direct measurement of the 3He+ magnetic moments.

Helium-3 has nowadays become one of the most important candidates for studies in fundamental physics1-3, nuclear and atomic structure4,5, magnetometry and metrology6, as well as chemistry and medicine7,8. In particular, 3He nuclear magnetic resonance (NMR) probes have been proposed as a new standard for absolute magnetometry6,9. This requires a high-accuracy value for the 3He nuclear magnetic moment, which, however, has so far been determined only indirectly and with a relative precision of 12 parts per billon10,11. Here we investigate the 3He+ ground-state hyperfine structure in a Penning trap to directly measure the nuclear g-factor of 3He+ [Formula: see text], the zero-field hyperfine splitting [Formula: see text] Hz and the bound electron g-factor [Formula: see text]. The latter is consistent with our theoretical value [Formula: see text] based on parameters and fundamental constants from ref. 12. Our measured value for the 3He+ nuclear g-factor enables determination of the g-factor of the bare nucleus [Formula: see text] via our accurate calculation of the diamagnetic shielding constant13 [Formula: see text]. This constitutes a direct calibration for 3He NMR probes and an improvement of the precision by one order of magnitude compared to previous indirect results. The measured zero-field hyperfine splitting improves the precision by two orders of magnitude compared to the previous most precise value14 and enables us to determine the Zemach radius15 to [Formula: see text] fm.

Multi-qubit entanglement and algorithms on a neutral-atom quantum computer.

Gate-model quantum computers promise to solve currently intractable computational problems if they can be operated at scale with long coherence times and high-fidelity logic. Neutral-atom hyperfine qubits provide inherent scalability owing to their identical characteristics, long coherence times and ability to be trapped in dense, multidimensional arrays1. Combined with the strong entangling interactions provided by Rydberg states2-4, all the necessary characteristics for quantum computation are available. Here we demonstrate several quantum algorithms on a programmable gate-model neutral-atom quantum computer in an architecture based on individual addressing of single atoms with tightly focused optical beams scanned across a two-dimensional array of qubits. Preparation of entangled Greenberger-Horne-Zeilinger (GHZ) states5 with up to six qubits, quantum phase estimation for a chemistry problem6 and the quantum approximate optimization algorithm (QAOA)7 for the maximum cut (MaxCut) graph problem are demonstrated. These results highlight the emergent capability of neutral-atom qubit arrays for universal, programmable quantum computation, as well as preparation of non-classical states of use for quantum-enhanced sensing.

Rewiring phospholipid biosynthesis reveals resilience to membrane perturbations and uncovers regulators of lipid homeostasis.

The organelles of eukaryotic cells differ in their membrane lipid composition. This heterogeneity is achieved by the localization of lipid synthesizing and modifying enzymes to specific compartments, as well as by intracellular lipid transport that utilizes vesicular and non-vesicular routes to ferry lipids from their place of synthesis to their destination. For instance, the major and essential phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC), can be produced by multiple pathways and, in the case of PE, also at multiple locations. However, the molecular components that underlie lipid homeostasis as well as the routes allowing their distribution remain unclear. Here, we present an approach in which we simplify and rewire yeast phospholipid synthesis by redirecting PE and PC synthesis reactions to distinct subcellular locations using chimeric enzymes fused to specific organelle targeting motifs. In rewired conditions, viability is expected to depend on homeostatic adaptation to the ensuing lipostatic perturbations and on efficient interorganelle lipid transport. We therefore performed genetic screens to identify factors involved in both of these processes. Among the candidates identified, we find genes linked to transcriptional regulation of lipid homeostasis, lipid metabolism, and transport. In particular, we identify a requirement for Csf1-an uncharacterized protein harboring a Chorein-N lipid transport motif-for survival under certain rewired conditions as well as lipidomic adaptation to cold, implicating Csf1 in interorganelle lipid transport and homeostatic adaptation.

Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.

Topological Insulator Metamaterials.

Confinement of electromagnetic fields at the subwavelength scale via metamaterial paradigms is an established method to engineer light-matter interaction in most common material systems, from insulators to semiconductors and from metals to superconductors. In recent years, this approach has been extended to the realm of topological materials, providing a new avenue to access nontrivial features of their electronic band structure. In this review, we survey various topological material classes from a photonics standpoint, including crystal growth and lithographic structuring methods. We discuss how exotic electronic features such as spin-selective Dirac plasmon polaritons in topological insulators or hyperbolic plasmon polaritons in Weyl semimetals may give rise to unconventional magneto-optic, nonlinear, and circular photogalvanic effects in metamaterials across the visible to infrared spectrum. Finally, we dwell on how these effects may be dynamically controlled by applying external perturbations in the form of electric and magnetic fields or ultrafast optical pulses. Through these examples and future perspectives, we argue that topological insulator, semimetal and superconductor metamaterials are unique systems to bridge the missing links between nanophotonic, electronic, and spintronic technologies.

Airway wall extracellular matrix changes induced by bronchial thermoplasty in severe asthma.

BACKGROUND: Airway remodeling is a prominent feature of asthma, which involves increased airway smooth muscle mass and altered extracellular matrix composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets airway remodeling. OBJECTIVE: We sought to investigate the effect of BT on extracellular matrix composition and its association with clinical outcomes. METHODS: This is a substudy of the TASMA trial. Thirty patients with severe asthma were BT-treated, of whom 13 patients were treated for 6 months with standard therapy (control group) before BT. Demographic data, clinical data including pulmonary function, and bronchial biopsies were collected. Biopsies at BT-treated and nontreated locations were analyzed by histological and immunohistochemical staining. Associations between histology and clinical outcomes were explored. RESULTS: Six months after treatment, it was found that the reticular basement membrane thickness was reduced from 7.28 µm to 5.74 µm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased by 2.5% and 5.9%, respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV1 reversibility. CONCLUSIONS: Besides reduction of airway smooth muscle mass, BT has an impact on reticular basement membrane thickness and the extracellular matrix arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV1 reversibility.

The impact of Zika emergence in remote communities in northwestern Ecuador.

The Zika virus (ZIKV) epidemic in Latin America (2015-2016) has primarily been studied in urban centers, with less understanding of its impact on smaller rural communities. To address this gap, we analyzed ZIKV sero-epidemiology in six rural Ecuadorian communities (2018-2019) with varying access to a commercial hub. Seroprevalence ranged from 19% to 54% measured by NS1 blockade of binding ELISA. We observed a decline in ZIKV seroprevalence between 2018 and 2019 that was greater among younger populations, suggesting that the attack rates in the 2015-16 epidemic were significantly higher than our 2018 observations. These data indicate that the 2015-16 epidemic included significant transmission in rural and more remote settings. Our observations of high seroprevalence in our area of study highlights the importance of surveillance and research in rural areas lacking robust health systems to manage future Zika outbreaks and vaccine initiatives.

Global burden of oral cancer in 2022 attributable to smokeless tobacco and areca nut consumption: a population attributable fraction analysis.

BACKGROUND: Consuming products that contain smokeless tobacco or areca nut increases the risk of oral cancer. We aimed to estimate the burden of oral cancer attributable to smokeless tobacco or areca nut consumption globally and by type of smokeless tobacco or areca nut product in four major consuming countries. METHODS: We calculated population attributable fractions (PAFs) using prevalence of current use of smokeless tobacco or areca nut products from national surveys and corresponding risks of oral cancer from the literature. We applied PAFs to national estimates of oral cancer incidence in 2022 from the Global Cancer Observatory's Cancer Today database to obtain cases attributable to smokeless tobacco or areca nut consumption. We modelled 95% uncertainty intervals (UIs) using Monte Carlo simulations. FINDINGS: Globally, an estimated 120 200 (95% UI 115 300-124 300) cases of oral cancer diagnosed in 2022 were attributable to smokeless tobacco or areca nut consumption, accounting for 30·8% (95% UI 29·6-31·9) of all oral cancer cases (120 200 of 389 800). An estimated 77% of attributable cases were among male patients (92 600 cases, 95% UI 88 000-96 500) and 23% were among female patients (27 600 cases, 26 000-29 000). Regions with the highest PAFs were Melanesia, Micronesia, and Polynesia (78·6%, 95% UI 74·4-80·5), southcentral Asia (57·5%, 54·8-59·5), and southeastern Asia (19·8%, 19·0-20·6). Lower-middle-income countries represented 90·2% of the world total attributable cases (108 400 cases, 95% UI 103 400-112 200). INTERPRETATION: Our findings suggest that one in three cases of oral cancer globally are attributable to smokeless tobacco or areca nut consumption, and could be prevented through smokeless tobacco and areca nut control. Global cancer control efforts must incorporate further measures to reduce smokeless tobacco and areca nut consumption in populations with the largest attributable burden. FUNDING: French National Cancer Institute.

Cold Spot SCANNER: Colab Notebook for predicting cold spots in protein-protein interfaces.

BACKGROUND: Protein-protein interactions (PPIs) are conveyed through binding interfaces or surface patches on proteins that become buried upon binding. Structural and biophysical analysis of many protein-protein interfaces revealed certain unique features of these surfaces that determine the energetics of interactions and play a critical role in protein evolution. One of the significant aspects of binding interfaces is the presence of binding hot spots, where mutations are highly deleterious for binding. Conversely, binding cold spots are positions occupied by suboptimal amino acids and several mutations in such positions could lead to affinity enhancement. While there are many software programs for identification of hot spot positions, there is currently a lack of software for cold spot detection. RESULTS: In this paper, we present Cold Spot SCANNER, a Colab Notebook, which scans a PPI binding interface and identifies cold spots resulting from cavities, unfavorable charge-charge, and unfavorable charge-hydrophobic interactions. The software offers a Py3DMOL-based interface that allows users to visualize cold spots in the context of the protein structure and generates a zip file containing the results for easy download. CONCLUSIONS: Cold spot identification is of great importance to protein engineering studies and provides a useful insight into protein evolution. Cold Spot SCANNER is open to all users without login requirements and can be accessible at: https://colab. RESEARCH: google.com/github/sagagugit/Cold-Spot-Scanner/blob/main/Cold_Spot_Scanner.ipynb .

Assessing different metrics of pedigree and genomic inbreeding and inbreeding effect on growth, fertility, and feed efficiency traits in a closed-herd Nellore cattle population.

BACKGROUND: The selection of individuals based on their predicted breeding values and mating of related individuals can increase the proportion of identical-by-descent alleles. In this context, the objectives of this study were to estimate inbreeding coefficients based on alternative metrics and data sources such as pedigree (FPED), hybrid genomic relationship matrix H (FH), and ROH of different length (FROH); and calculate Pearson correlations between the different metrics in a closed Nellore cattle population selected for body weight adjusted to 378 days of age (W378). In addition to total FROH (all classes) coefficients were also estimated based on the size class of the ROH segments: FROH1 (1-2 Mb), FROH2 (2-4 Mb), FROH3 (4-8 Mb), FROH4 (8-16 Mb), and FROH5 (> 16 Mb), and for each chromosome (FROH_CHR). Furthermore, we assessed the effect of each inbreeding metric on birth weight (BW), body weights adjusted to 210 (W210) and W378, scrotal circumference (SC), and residual feed intake (RFI). We also evaluated the chromosome-specific effects of inbreeding on growth traits. RESULTS: The correlation between FPED and FROH was 0.60 while between FH and FROH and FH and FPED were 0.69 and 0.61, respectively. The annual rate of inbreeding was 0.16% for FPED, 0.02% for FH, and 0.16% for FROH. A 1% increase in FROH5 resulted in a reduction of up to -1.327 ± 0.495 kg in W210 and W378. Four inbreeding coefficients (FPED, FH, FROH2, and FROH5) had a significant effect on W378, with reductions of up to -3.810 ± 1.753 kg per 1% increase in FROH2. There was an unfavorable effect of FPED on RFI (0.01 ± 0.0002 kg dry matter/day) and of FROH on SC (-0.056 ± 0.022 cm). The FROH_CHR coefficients calculated for BTA3, BTA5, and BTA8 significantly affected the growth traits. CONCLUSIONS: Inbreeding depression was observed for all traits evaluated. However, these effects were greater for the criterion used for selection of the animals (i.e., W378). The increase in the genomic inbreeding was associated with a higher inbreeding depression on the traits evaluated when compared to pedigree-based inbreeding. Genomic information should be used as a tool during mating to optimize control of inbreeding and, consequently, minimize inbreeding depression in Nellore cattle.

Genome-wide association study between copy number variation and feeding behavior, feed efficiency, and growth traits in Nellore cattle.

BACKGROUND: Feeding costs represent the largest expenditures in beef production. Therefore, the animal efficiency in converting feed in high-quality protein for human consumption plays a major role in the environmental impact of the beef industry and in the beef producers' profitability. In this context, breeding animals for improved feed efficiency through genomic selection has been considered as a strategic practice in modern breeding programs around the world. Copy number variation (CNV) is a less-studied source of genetic variation that can contribute to phenotypic variability in complex traits. In this context, this study aimed to: (1) identify CNV and CNV regions (CNVRs) in the genome of Nellore cattle (Bos taurus indicus); (2) assess potential associations between the identified CNVR and weaning weight (W210), body weight measured at the time of selection (WSel), average daily gain (ADG), dry matter intake (DMI), residual feed intake (RFI), time spent at the feed bunk (TF), and frequency of visits to the feed bunk (FF); and, (3) perform functional enrichment analyses of the significant CNVR identified for each of the traits evaluated. RESULTS: A total of 3,161 CNVs and 561 CNVRs ranging from 4,973 bp to 3,215,394 bp were identified. The CNVRs covered up to 99,221,894 bp (3.99%) of the Nellore autosomal genome. Seventeen CNVR were significantly associated with dry matter intake and feeding frequency (number of daily visits to the feed bunk). The functional annotation of the associated CNVRs revealed important candidate genes related to metabolism that may be associated with the phenotypic expression of the evaluated traits. Furthermore, Gene Ontology (GO) analyses revealed 19 enrichment processes associated with FF. CONCLUSIONS: A total of 3,161 CNVs and 561 CNVRs were identified and characterized in a Nellore cattle population. Various CNVRs were significantly associated with DMI and FF, indicating that CNVs play an important role in key biological pathways and in the phenotypic expression of feeding behavior and growth traits in Nellore cattle.

Chronic central nervous system leptin administration attenuates kidney dysfunction and injury in a model of ischemia/reperfusion-induced acute kidney injury.

In the present study we examined whether chronic intracerebroventricular (ICV) leptin administration protects against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Twelve-week-old male rats were implanted with an ICV cannula into the right lateral ventricle and 8-10 days after surgery, leptin (0.021 mg/hr, n=8) or saline vehicle (0.5 ml/h, n=8) was infused via osmotic minipump connected to the ICV cannula for 12 days. On day 8 of leptin or vehicle infusion, rats were submitted to unilateral ischemia/reperfusion (UIR) by clamping the left pedicle for 30 min. To control for leptin-induced reductions in food intake, the vehicle-treated group was pair-fed (UIR-PF) to match the same amount of food consumed by leptin-treated (UIR-Leptin) rats. On the 12th day of leptin or vehicle infusion (4th day after AKI), single-left kidney glomerular filtration rate (GFR) was measured, blood samples were collected to quantify white blood cells, and kidneys were collected for histological assessment of injury. UIR-Leptin treated rats showed reduced right and left kidney weights (right: 1040±24 vs. 1281±36 mg; left: 1127±71 vs. 1707±45 mg, for UIR-Leptin and UIR-PF, respectively). ICV leptin infusion improved GFR (0.50±0.06 vs. 0.13±0.03 ml/min/g KW) and reduced kidney injury scores. ICV leptin treatment also attenuated the reduction in circulating adiponectin levels that was observed in UIR-PF rats, and increased circulating white blood cells count compared to UIR-PF rats (16.3±1.3 vs. 9.8±0.6 k/mL). Therefore, we show that leptin, via its actions on the central nervous system, confers significant protection against major kidney dysfunction and injury in a model of ischemia/reperfusion-induced AKI.

Parental obesity predisposes offspring to kidney dysfunction and increased susceptibility to ischemia-reperfusion injury in a sex-dependent manner.

Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.

Outcomes from the International Society of Nephrology Haemolytic Uraemic Syndromes International Forum.

The haemolytic uraemic syndromes (HUS) are a heterogeneous group of conditions only some of which are mediated by complement (CaHUS). We report the outcome of the 2023 International Society of Nephrology HUS International Forum where a global panel of experts considered the current state of the art, identified areas of uncertainty, and proposed optimal solutions. Areas of uncertainty and areas for future research included: the nomenclature of HUS; novel complement testing strategies; identification of biomarkers; genetic predisposition to aHUS; optimal dosing and withdrawal strategies for C5 inhibitors; treatment of kidney transplantation recipients; disparity of access to treatment; and the next generation of complement inhibitors in CaHUS. The current rationale for optimal patient management is described.

Airway smooth muscle and long-term clinical efficacy following bronchial thermoplasty in severe asthma.

The mechanism of action of bronchial thermoplasty (BT) treatment for patients with severe asthma is incompletely understood. This study investigated the 2.5-year impact of BT on airway smooth muscle (ASM) mass and clinical parameters by paired data analysis in 22 patients. Our findings demonstrate the persistence of ASM mass reduction of >50% after 2.5 years. Furthermore, sustained improvement in asthma control, quality of life and exacerbation rates was found, which is in line with previous reports. An association was found between the remaining ASM and both the exacerbation rate (r=0.61, p=0.04 for desmin, r=0.85, p<0.01 for alpha smooth muscle actin (SMA)) and post-bronchodilator forced expiratory volume in 1 s predicted percentage (r=-0.69, p=0.03 for desmin, r=-0.58, p=0.08 for alpha SMA). This study provides new insight into the long-term impact of BT.

The impact of adverse childhood experiences on multimorbidity: a systematic review and meta-analysis.

BACKGROUND: Adverse childhood experiences (ACEs) have been implicated in the aetiology of a range of health outcomes, including multimorbidity. In this systematic review and meta-analysis, we aimed to identify, synthesise, and quantify the current evidence linking ACEs and multimorbidity. METHODS: We searched seven databases from inception to 20 July 2023: APA PsycNET, CINAHL Plus, Cochrane CENTRAL, Embase, MEDLINE, Scopus, and Web of Science. We selected studies investigating adverse events occurring during childhood (< 18 years) and an assessment of multimorbidity in adulthood (≥ 18 years). Studies that only assessed adverse events in adulthood or health outcomes in children were excluded. Risk of bias was assessed using the ROBINS-E tool. Meta-analysis of prevalence and dose-response meta-analysis methods were used for quantitative data synthesis. This review was pre-registered with PROSPERO (CRD42023389528). RESULTS: From 15,586 records, 25 studies were eligible for inclusion (total participants = 372,162). The prevalence of exposure to ≥ 1 ACEs was 48.1% (95% CI 33.4 to 63.1%). The prevalence of multimorbidity was 34.5% (95% CI 23.4 to 47.5%). Eight studies provided sufficient data for dose-response meta-analysis (total participants = 197,981). There was a significant dose-dependent relationship between ACE exposure and multimorbidity (p < 0.001), with every additional ACE exposure contributing to a 12.9% (95% CI 7.9 to 17.9%) increase in the odds for multimorbidity. However, there was heterogeneity among the included studies (I2 = 76.9%, Cochran Q = 102, p < 0.001). CONCLUSIONS: This is the first systematic review and meta-analysis to synthesise the literature on ACEs and multimorbidity, showing a dose-dependent relationship across a large number of participants. It consolidates and enhances an extensive body of literature that shows an association between ACEs and individual long-term health conditions, risky health behaviours, and other poor health outcomes.

Genomic description of acquired fluconazole- and echinocandin-resistance in patients with serial Candida glabrata isolates.

Candida glabrata is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient. Phylogenetic analysis demonstrated that isolates from 29 patients were clustered by patient. The median SNPs between isolates from the same patient was 30 (range: 7-96 SNPs), while unrelated strains infected four patients. Twenty-one isolates were resistant to echinocandins, and 24 were resistant to fluconazole. All echinocandin-resistant isolates carried a mutation either in the FKS1 or FKS2 HS1 region. Of the 24 fluconazole-resistant isolates, 17 (71%) had non-synonymous polymorphisms in the PDR1 gene, which were absent in susceptible isolates. In 11 patients, a genetically related resistant isolate was collected after recovering susceptible isolates, indicating in vivo acquisition of resistance. These findings allowed us to estimate the intra-host diversity of C. glabrata and propose an upper boundary of 96 SNPs for defining genetically related isolates, which can be used to assess donor-to-host transmission, nosocomial transmission, or acquired resistance. IMPORTANCE In our study, mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrata isolates using a whole-genome sequence. C. glabrata is the second most common cause of candidemia in the United States, which rapidly acquires resistance to antifungals, in vitro and in vivo.

Early postnatal development of the primary visual areas 17 and 18 of the cat cerebral cortex: An SMI-32 study.

Using anti-neurofilament H non-phosphorylated antibodies (SMI-32) as markers for the neuronal maturation level and Y channel responsible for motion processing, we investigated early postnatal development of the primary visual areas 17 and 18 in cats aged 0, 10, 14, and 34 days and in adults. Two analyzed parameters of SMI-32-immunolabeling were used: the total proportion of SMI-32-labeling and the density of labeled neurons. (i) The developmental time course of the total proportion of SMI-32-labeling shows the general increase in the accumulation of heavy-chain neurofilaments. This parameter showed a different time course for cortical layer development; the maximal increment in the total labeling in layer V occurred between the second and fifth postnatal weeks and in layers II-III and VI after the fifth postnatal week. In addition, the delay in accumulation of SMI-32-labeling was shown in layer V of the area 17 periphery representation during the first two postnatal weeks. (ii) The density of SMI-32-labeled neurons decreased in all layers of area 18, but was increased, decreased, or had a transient peak in layers II-III, V, and VI of area 17, respectively. The transient peak is in good correspondence with some transient neurochemical features previously revealed for different classes of cortical and thalamic neurons and reflects the time course of the early development of the thalamocortical circuitry. Some similarities between the time courses for the development of SMI-32-labeling in areas 17/18 and in A- and C-laminae of the LGNd allow us to propose heterochronous postnatal development of two Y sub-channels.

Tuberculosis caused by Mycobacterium africanum: Knowns and unknowns.

Tuberculosis (TB), one of the deadliest threats to human health, is mainly caused by 2 highly related and human-adapted bacteria broadly known as Mycobacterium tuberculosis and Mycobacterium africanum. Whereas M. tuberculosis is widely spread, M. africanum is restricted to West Africa, where it remains a significant cause of tuberculosis. Although several differences have been identified between these 2 pathogens, M. africanum remains a lot less studied than M. tuberculosis. Here, we discuss the genetic, phenotypic, and clinical similarities and differences between strains of M. tuberculosis and M. africanum. We also discuss our current knowledge on the immune response to M. africanum and how it possibly articulates with distinct disease progression and with the geographical restriction attributed to this pathogen. Understanding the functional impact of the diversity existing in TB-causing bacteria, as well as incorporating this diversity in TB research, will contribute to the development of better, more specific approaches to tackle TB.