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The fate of residual graphite derived from hydrometallurgical treatment of spent Lithium-ion batteries remains uncertain. This study dwells on the aim of identifying the potentialities of recycling residual graphite for wastewater treatment. Graphite was recovered hydrometallurgically, and new adsorption materials: graphite oxide (GO) and graphene oxide (GrO) were synthesized from the residual graphite using the chemical oxidization method. Synthesized materials showed higher interlayer spacings (GO = 0.81 nm, GrO = 0.78 nm) than the commercially available similar materials. Adsorption studies revealed higher adsorption capacities for both dye (>550 mg/g in all cases) and metal ions (highest ∼93 mg/g for Ni2+ and lowest ∼68 mg/g for Zn2+). GrO showed superior results than GO due to its high surface area and porosity despite GO having more functional groups. Moreover, produced materials showed about 97 % removal of dye and about 94 % removal of contaminated metals which are higher performance than existing commercial or similar materials. These findings highlight the promising recycling capabilities of waste graphite and suggest its potential as a substitute for natural graphite.

Summary: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adults. Depolarizing GABA responses have been well characterized at neuronal-population average level during typical neurodevelopment and partially in brain disorders. However, no investigation has specifically assessed whether a mosaicism of cells with either depolarizing or hyperpolarizing/inhibitory GABAergic responses exists in animals in health/disease at diverse developmental stages, including adulthood. Here, we showed that such mosaicism is present in wild-type (WT) and down syndrome (DS) neuronal networks, as assessed at increasing scales of complexity (cultures, brain slices, behaving mice). Nevertheless, WT mice presented a much lower percentage of cells with depolarizing GABA than DS mice. Restoring the mosaicism of hyperpolarizing and depolarizing GABA-responding neurons to WT levels rescued anxiety behavior in DS mice. Moreover, we found heterogeneous GABAergic responses in developed control and trisomic human induced-pluripotent-stem-cells-derived neurons. Thus, a heterogeneous subpopulation of GABA-responding cells exists in physiological/pathological conditions in mouse and human neurons, possibly contributing to disease-associated behaviors.

Suicidal ideation and behavior have a marked prevalence in several cluster B personality disorders (e.g., Borderline and narcissistic personality disorders according to the last versions of the Diagnostic and Statistical Manual for Mental Disorders), compared to others. Intense feelings of shame can often be found in individuals with narcissistic personality disorder and may play a role in suicidal behavior. To explore the relationship between narcissism, shame and suicide ideation, Pathological Narcissism Inventory, Test of Self Conscious Affects and Beck Scale for Suicidal Ideation were administered to a sample of individuals with suicide ideation (N = 68; Mage=35,18, SD=15,62; 44,1 % males) and a sample of community participants (N = 153; Mage=27,41, SD=12,17; 41,2 % males). Controlling for age and gender, we found that Beck Scale for Suicidal Ideation scores were significantly associated with narcissistic vulnerability and interpersonal shame. In the clinical sample, interpersonal shame partially mediated the relationship between the vulnerability facet of narcissism and suicidal ideation. Shame seems to have a crucial role in the relationship between the vulnerability facet of narcissism and suicidal ideation, although its complex influence remains to be understood. Clinicians may want to pay attention to intense shame feelings in individuals with vulnerable narcissism that may lead to decompensation and increase suicide risk.

A reliable determination of equivalent black carbon (eBC) mass concentrations derived from filter absorption photometers (FAPs) measurements depends on the appropriate quantification of the mass absorption cross-section (MAC) for converting the absorption coefficient (babs) to eBC. This study investigates the spatial–temporal variability of the MAC obtained from simultaneous elemental carbon (EC) and babs measurements performed at 22 sites. We compared different methodologies for retrieving eBC integrating different options for calculating MAC including: locally derived, median value calculated from 22 sites, and site-specific rolling MAC. The eBC concentrations that underwent correction using these methods were identified as LeBC (local MAC), MeBC (median MAC), and ReBC (Rolling MAC) respectively. Pronounced differences (up to more than 50 %) were observed between eBC as directly provided by FAPs (NeBC; Nominal instrumental MAC) and ReBC due to the differences observed between the experimental and nominal MAC values. The median MAC was 7.8 ± 3.4 m2 g-1 from 12 aethalometers at 880 nm, and 10.6 ± 4.7 m2 g-1 from 10 MAAPs at 637 nm. The experimental MAC showed significant site and seasonal dependencies, with heterogeneous patterns between summer and winter in different regions. In addition, long-term trend analysis revealed statistically significant (s.s.) decreasing trends in EC. Interestingly, we showed that the corresponding corrected eBC trends are not independent of the way eBC is calculated due to the variability of MAC. NeBC and EC decreasing trends were consistent at sites with no significant trend in experimental MAC. Conversely, where MAC showed s.s. trend, the NeBC and EC trends were not consistent while ReBC concentration followed the same pattern as EC. These results underscore the importance of accounting for MAC variations when deriving eBC measurements from FAPs and emphasize the necessity of incorporating EC observations to constrain the uncertainty associated with eBC.

This study addressed the scarcity of NH3 measurements in urban Europe and the diverse monitoring protocols, hindering direct data comparison. Sixty-nine datasets from Finland, France, Italy, Spain, and the UK across various site types, including industrial (IND, 8), traffic (TR, 12), urban (UB, 22), suburban (SUB, 12), and regional background (RB, 15), are analyzed to this study. Among these, 26 sites provided 5, or more, years of data for time series analysis. Despite varied protocols, necessitating future harmonization, the average NH3 concentration across sites reached 8.0 ± 8.9 μg/m3. Excluding farming/agricultural hotspots (FAHs), IND and TR sites had the highest concentrations (4.7 ± 3.2 and 4.5 ± 1.0 μg/m3), followed by UB, SUB, and RB sites (3.3 ± 1.5, 2.7 ± 1.3, and 1.0 ± 0.3 μg/m3, respectively) indicating that industrial, traffic, and other urban sources were primary contributors to NH3 outside FAH regions. When referring exclusively to the FAHs, concentrations ranged from 10.0 ± 2.3 to 15.6 ± 17.2 μg/m3, with the highest concentrations being reached in RB sites close to the farming and agricultural sources, and that, on average for FAHs there is a decreasing NH3 concentration gradient towards the city. Time trends showed that over half of the sites (18/26) observed statistically significant trends. Approximately 50 % of UB and TR sites showed a decreasing trend, while 30 % an increasing one. Meta-analysis revealed a small insignificant decreasing trend for non-FAH RB sites. In FAHs, there was a significant upward trend at a rate of 3.51[0.45,6.57]%/yr. Seasonal patterns of NH3 concentrations varied, with urban areas experiencing fluctuations influenced by surrounding emissions, particularly in FAHs. Diel variation showed differing patterns at urban monitoring sites, all with higher daytime concentrations, but with variations in peak times depending on major emission sources and meteorological patterns. These results offer valuable insights into the spatio-temporal patterns of gas-phase NH3 concentrations in urban Europe, contributing to future efforts in benchmarking NH3 pollution control in urban areas.

For a Positive Matrix Factorization (PMF) aerosol source apportionment (SA) studies there is no standard procedure to select the most appropriate chemical components to be included in the input dataset for a given site typology, nor specific recommendations in this direction. However, these choices are crucial for the final SA outputs not only in terms of number of sources identified but also, and consequently, in the source contributions estimates. In fact, PMF tends to reproduce most of PM mass measured independently and introduced as a total variable in the input data, regardless of the percentage of PM mass which has been chemically characterized, so that the lack of some specific source tracers (e.g. levoglucosan) can potentially affect the results of the whole source apportionment study. The present study elaborates further on the same concept, evaluating quantitatively the impact of lacking specific sources’ tracers on the whole source apportionment, both in terms of identified sources and source contributions. This work aims to provide first recommendations on the most suitable and critical components to be included in PMF analyses in order to reduce PMF output uncertainty as much as possible, and better represent the most commons PM sources observed in many sites in Western countries. To this aim, we performed three sensitivity analyses on three different datasets across EU, including extended sets of organic tracers, in order to cover different types of urban conditions (Mediterranean, Continental, and Alpine), source types, and PM fractions. Our findings reveal that the vehicle exhaust source resulted to be less sensitive to the choice of analytes, although source contributions estimates can deviate significantly up to 44 %. On the other hand, for the detection of the non-exhaust one is clearly necessary to analyze specific inorganic elements. The choice of not analysing non-polar organics likely causes the loss of separation of exhaust and non-exhaust factors, thus obtaining a unique road traffic source, which provokes a significant bias of total contribution. Levoglucosan was, in most cases, crucial to identify biomass burning contributions in Milan and in Barcelona, in spite of the presence of PAHs in Barcelona, while for the case of Grenoble, even discarding levoglucosan, the presence of PAHs allowed identifying the BB factor. Modifying the rest of analytes provoke a systematic underestimation of biomass burning source contributions. SIA factors resulted to be generally overestimated with respect to the base case analysis, also in the case that ions were not included in the PMF analysis. Trace elements were crucial to identify shipping emissions (V and Ni) and industrial sources (Pb, Ni, Br, Zn, Mn, Cd and As). When changing the rest of input variables, the uncertainty was narrow for shipping but large for industrial processes. Major and trace elements were also crucial to identify the mineral/soil factor at all cities. Biogenic SOA and Anthropogenic SOA factors were sensitive to the presence of their molecular tracers, since the availability of OC alone is unable to separate a SOA factor. Arabitol and sorbitol were crucial to detecting fungal spores while odd number of higher alkanes (C27 to C31) for plant debris.

Summary: Magnetic nanoparticles can be functionalized in many ways for biomedical applications. Here, we combine four advantageous features in a novel Fe-Pt-Yb2O3 core-shell nanoparticle. (a) The nanoparticles have a size of 10 nm allowing them to diffuse through neuronal tissue. (b) The particles are superparamagnetic after synthesis and ferromagnetic after annealing, enabling directional control by magnetic fields, enhance NMRI contrast, and hyperthermia treatment. (c) After neutron-activation of the shell, they carry low-energetic, short half-life β-radiation from 175Yb, 177Yb, and 177Lu. (d) Additionally, the particles can be optically visualized by plasmonic excitation and luminescence. To demonstrate the potential of the particles for cancer treatment, we exposed cultured human glioblastoma cells (LN-18) to non-activated and activated particles to confirm that the particles are internalized, and that the β-radiation of the radioisotopes incorporated in the neutron-activated shell of the nanoparticles kills more than 98% of the LN-18 cancer cells, promising for future anti-cancer applications.

This study analyzed the variability of equivalent black carbon (eBC) mass concentrations and their sources in urban Europe to provide insights into the use of eBC as an advanced air quality (AQ) parameter for AQ standards. This study compiled eBC mass concentration datasets covering the period between 2006 and 2022 from 50 measurement stations, including 23 urban background (UB), 18 traffic (TR), 7 suburban (SUB), and 2 regional background (RB) sites. The results highlighted the need for the harmonization of eBC measurements to allow for direct comparisons between eBC mass concentrations measured across urban Europe. The eBC mass concentrations exhibited a decreasing trend as follows: TR > UB > SUB > RB. Furthermore, a clear decreasing trend in eBC concentrations was observed in the UB sites moving from Southern to Northern Europe. The eBC mass concentrations exhibited significant spatiotemporal heterogeneity, including marked differences in eBC mass concentration and variable contributions of pollution sources to bulk eBC between different cities. Seasonal patterns in eBC concentrations were also evident, with higher winter concentrations observed in a large proportion of cities, especially at UB and SUB sites. The contribution of eBC from fossil fuel combustion, mostly traffic (eBCT) was higher than that of residential and commercial sources (eBCRC) in all European sites studied. Nevertheless, eBCRC still had a substantial contribution to total eBC mass concentrations at a majority of the sites. eBC trend analysis revealed decreasing trends for eBCT over the last decade, while eBCRC remained relatively constant or even increased slightly in some cities.

Objective: Adipose tissue, via sympathetic and possibly sensory neurons, communicates with the central nervous system (CNS) to mediate energy homeostasis. In contrast to the sympathetic nervous system, the morphology, role and regulation of the sensory nervous system in adipose tissue are poorly characterized. Methods and results: Taking advantage of recent progress in whole-mount three-dimensional imaging, we identified a network of calcitonin gene-related protein (CGRP)-positive sensory neurons in murine white adipose tissue (WAT). We found that adipose mammalian target of rapamycin complex 2 (mTORC2), a major component of the insulin signaling pathway, is required for arborization of sensory neurons, but not of sympathetic neurons. Time course experiments revealed that adipose mTORC2 is required for maintenance of sensory neurons. Furthermore, loss of sensory innervation in WAT coincided with systemic insulin resistance. Finally, we established that neuronal protein growth-associated protein 43 (GAP43) is a marker for sensory neurons in adipose tissue. Conclusion: Our findings indicate that adipose mTORC2 is necessary for sensory innervation in WAT. In addition, our results suggest that WAT may affect whole-body energy homeostasis via sensory neurons.

TAK1 is a serine threonine kinase that mediates signal transduction induced by TGFβ and bone morphogenetic proteins, and controls a variety of cell functions by modulating the downstream activation of NF-kkB, JNK, and p38. Heterozygous variants in the coding MAP3K7 gene cause the cardiospondylocarpofacial syndrome, characterized by various abnormalities. Skin fibroblasts derived from a patient carrying the MAP3K7 c.737-7A>G heterozygous variant were reprogrammed using Sendai viral vector system carrying the Yamanaka factors. The generated induced pluripotent stem cells (iPSC) line retained the original genotype, expressed pluripotency markers, and differentiated into cells of the three germ layers.

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant (AD) genetic trait characterized by elevated basal serum tryptase ≥8 ng/mL, caused by increased α-tryptase-encoding TPSAB1 copy number. HαT affects 5% to 7% of Western populations and has been associated with joint hypermobility. Hypermobility disorders are likewise frequently AD, but genetic etiologies are often elusive. Genotyping of individuals with hypermobility spectrum disorder (n = 132), hypermobile Ehlers-Danlos syndrome (n = 78), or axial skeletal abnormalities with hypermobility (n = 56) was performed. Clinical features of individuals with and without HαT were compared. When analyzing our combined cohorts, dysphagia (p = 0.007) and retained primary dentition (p = 0.0003) were significantly associated with HαT, while positive associations with anaphylaxis (p = 0.07) and pruritus (P = 0.5) did not reach significance likely due to limited sample size. Overall, HαT prevalence is not increased in individuals with hypermobility disorders, rather linked to a unique endotype, demonstrating how HαT may modify clinical presentations of complex patients.

Raw cotton fabrics contain natural impurities (fats, waxes, pectins, and proteins), which impart hydrophobic nature and interfere with textile dyeing. Typically, these noncellulosic impurities are removed by alkaline scouring with hot aqueous sodium hydroxide. As a greener alternative with reduced environmental impact, enzymes can be used to improve cotton hydrophilicity and the quality of fabrics. Thus, this study aimed to establish a roadmap for bioscouring of knitted cotton fabrics using a commercial pectinase preparation under mild conditions of pH and temperature. Pectate lyase (1–10 g L−1) was applied for 30 min at 55 °C at optimum pH 8.5, evaluating different post-treatments with varying temperature and surfactant concentration. The treated samples were characterized in terms of weight loss, water absorption, pectin content, whiteness index, and FTIR spectra. A high level of cleaning was achieved, with an efficacy comparable to conventional alkaline scouring. It was possible to increase the wettability of the textile article with a reduction in fiber damage and in the consumption of energy, water, and chemicals. Low surfactant concentration (0.2 g L−1) and 70 °C washing temperature in the post-washing step were found sufficient to aid in the removal of waxes and fats from the cotton surface after bioscouring and were adequate to achieve high hydrophilicity at low weight loss, unlike other bioscouring studies that used temperatures equal or higher than 80 °C. Results clearly proved that the efficiency of bioscouring to achieve suitable wettability of knitted cotton fabrics depends essentially on an effective post-washing step and the selected conditions, which impact the sustainability and economic viability of the whole process.

Introduction: Neuroendocrine tumors (NETs) are rare and malignant neoplasms characterized by their potential to produce metabolically active substances with the capacity to bring about clinical syndromes. The clinical expression of serotonin-producing NETs is known as carcinoid syndrome (CS). The synthesis of serotonin in the brain is dependent on tryptophan availability. At the central level, serotonin is indispensable for mood, anxiety, and sleep regulation. In CS patients, around 60% of all tryptophan is reported to be consumed by tumor cells for the peripheral synthesis of serotonin, increasing the risk of a central deficiency and thus psychiatric disorders. Materials and methods: This manuscript reviews the existing literature about psychiatric disorders associated with NETs and addresses the safety of psychiatric drugs in these patients. A systematic search of the biomedical literature was performed using the following databases: PubMed, Embase, CINAHL (EBSCO), PsycInfo (OVID), and Cochrane CENTRAL (Wiley). The database search included articles published between January 1965 and February 2021. Relevant information were charted using a calibrated charting-form. Results: Twenty-two articles were included in the present review. The overall population size of the studies came to 3319 patients. All patients presented a confirmed diagnosis of NET. The information about the presence of CS was confirmed in 351 cases. The psychiatric symptoms reported included mood disturbances (including, depression and anxiety), psychoses, impulse control disorders and sleeping alterations. We also evaluated the presence of cognitive impairments in NET patients. Finally, we summarize the available data regarding the safety of psychiatric drugs in this setting. Conclusions: Psychiatric disorders among NET patients are poorly recognized, and therefore have received very little research attention. As a result, no standardized algorithm is presently available. Our findings support detailed psychiatric evaluation in NET patients, especially in those presenting CS and symptoms suggestive of psychiatric involvement. Not only do cognitive impairment and psychiatry symptoms negatively impact health-related quality of life in cancer patients, they can also reduce survival rates.

Summary: Recent advances in bioelectronics and neural engineering allowed the development of brain machine interfaces and neuroprostheses, capable of facilitating or recovering functionality in people with neurological disability. To realize energy-efficient and real-time capable devices, neuromorphic computing systems are envisaged as the core of next-generation systems for brain repair. We demonstrate here a real-time hardware neuromorphic prosthesis to restore bidirectional interactions between two neuronal populations, even when one is damaged or missing. We used in vitro modular cell cultures to mimic the mutual interaction between neuronal assemblies and created a focal lesion to functionally disconnect the two populations. Then, we employed our neuromorphic prosthesis for bidirectional bridging to artificially reconnect two disconnected neuronal modules and for hybrid bidirectional bridging to replace the activity of one module with a real-time hardware neuromorphic Spiking Neural Network. Our neuroprosthetic system opens avenues for the exploitation of neuromorphic-based devices in bioelectrical therapeutics for health care. : Neuroscience; Systems Neuroscience; Computer Science; Evolvable Hardware; Electronic Materials Subject Areas: Neuroscience, Systems Neuroscience, Computer Science, Evolvable Hardware, Electronic Materials

Objectives: Posterior Cortical Atrophy (PCA) is an atypical presentation of Alzheimer disease (AD) characterized by atrophy of posterior brain regions. This pattern of atrophy is usually evaluated with Koedam visual rating scale, a score developed to enable visual assessment of parietal atrophy on magnetic resonance imaging (MRI). However, Koedam scale is complex to assess and its utility in the differential diagnosis between PCA and typical AD has not been demonstrated yet. The aim of this study is therefore to spot a simple and reliable MRI element able to differentiate between PCA and typical AD using visual rating scales. Methods: 15 patients who presented with progressive complex visual disorders and predominant occipitoparietal hypometabolism on PET-FDG were selected from our centre and compared with 30 typical AD patients and 15 healthy subjects. We used previously validated visual rating scales including Koedam scale, which we divided into three major components: posterior cingulate, precuneus and parieto-occipital. Subsequently we validated the results using the automated software Brainvisa Morphologist and Voxel Based Morphometry (VBM). Results: Patients with PCA, compared to typical AD, showed higher widening of the parieto-occipital sulcus, assessed both with visual rating scales and Brainvisa. In the corresponding areas, the VBM analysis showed an inverse correlation between the results obtained from the visual evaluation scales with the volume of the grey matter and a direct correlation between the same results with the cerebrospinal fluid volume. Conclusions: A visually based rating scale for parieto-occipital sulcus can distinguish Posterior Cortical Atrophy from typical Alzheimer disease.

In this study, the performance of two types of source apportionment models was evaluated by assessing the results provided by 40 different groups in the framework of an intercomparison organised by FAIRMODE WG3 (Forum for air quality modelling in Europe, Working Group 3). The evaluation was based on two performance indicators: z-scores and the root mean square error weighted by the reference uncertainty (RMSEu), with pre-established acceptability criteria. By involving models based on completely different and independent input data, such as receptor models (RMs) and chemical transport models (CTMs), the intercomparison provided a unique opportunity for their cross-validation. In addition, comparing the CTM chemical profiles with those measured directly at the source contributed to corroborate the consistency of the tested model results. The most commonly used RM was the US EPA- PMF version 5. RMs showed very good performance for the overall dataset (91% of z-scores accepted) while more difficulties were observed with the source contribution time series (72% of RMSEu accepted). Industrial activities proved to be the most difficult sources to be quantified by RMs, with high variability in the estimated contributions. In the CTMs, the sum of computed source contributions was lower than the measured gravimetric PM10 mass concentrations. The performance tests pointed out the differences between the two CTM approaches used for source apportionment in this study: brute force (or emission reduction impact) and tagged species methods. The sources meeting the z-score and RMSEu acceptability criteria tests were 50% and 86%, respectively. The CTM source contributions to PM10 were in the majority of cases lower than the RM averages for the corresponding source. The CTMs and RMs source contributions for the overall dataset were more comparable (83% of the z-scores accepted) than their time series (successful RMSEu in the range 25% - 34%). The comparability between CTMs and RMs varied depending on the source: traffic/exhaust and industry were the source categories with the best results in the RMSEu tests while the most critical ones were soil dust and road dust. The differences between RMs and CTMs source reconstructions confirmed the importance of cross validating the results of these two families of models. Keywords: Source apportionment, PM10, Receptor models, Chemical transport models, Intercomparison, Lens

Summary: Highly glycolytic cancer cells prevent intracellular acidification by excreting the glycolytic end-products lactate and H+ via the monocarboxylate transporters 1 (MCT1) and 4 (MCT4). We report that syrosingopine, an anti-hypertensive drug, is a dual MCT1 and MCT4 inhibitor (with 60-fold higher potency on MCT4) that prevents lactate and H+ efflux. Syrosingopine elicits synthetic lethality with metformin, an inhibitor of mitochondrial NADH dehydrogenase. NAD+, required for the ATP-generating steps of glycolysis, is regenerated from NADH by mitochondrial NADH dehydrogenase or lactate dehydrogenase. Syrosingopine treatment leads to high intracellular lactate levels and thereby end-product inhibition of lactate dehydrogenase. The loss of NAD+ regeneration capacity due to combined metformin and syrosingopine treatment results in glycolytic blockade, leading to ATP depletion and cell death. Accordingly, ATP levels can be partly restored by exogenously provided NAD+, the NAD precursor nicotinamide mononucleotide (NMN), or vitamin K2. Thus, pharmacological inhibition of MCT1 and MCT4 combined with metformin treatment is a potential cancer therapy. : Benjamin et al. show that the clinical drug syrosingopine potently inhibits the lactate transporters MCT1 and MCT4 and is thus a clinically relevant MCT4 inhibitor. Intracellular lactate accumulation by syrosingopine elicits synthetic lethality with metformin and potentiates metformin’s anti-cancer efficacy. Keywords: cancer, metformin, syrosingopine, lactate, MCT1, MCT4, synthetic lethality

Mutations in B3GALT6, encoding the galactosyltransferase II (GalT-II) involved in the synthesis of the glycosaminoglycan (GAG) linkage region of proteoglycans (PGs), have recently been associated with a spectrum of connective tissue disorders, including spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) and Ehlers–Danlos-like syndrome. Here, we report on two sisters compound heterozygous for two novel B3GALT6 mutations that presented with severe short stature and progressive kyphoscoliosis, joint hypermobility and laxity, hyperextensible skin, platyspondyly, short ilia, and elbow malalignment. Microarray-based transcriptome analysis revealed the differential expression of several genes encoding extracellular matrix (ECM) structural components, including COMP, SPP1, COL5A1, and COL15A1, enzymes involved in GAG synthesis and in ECM remodeling, such as CSGALNACT1, CHPF, LOXL3, and STEAP4, signaling transduction molecules of the TGFβ/BMP pathway, i.e., GDF6, GDF15, and BMPER, and transcription factors of the HOX and LIM families implicated in skeletal and limb development. Immunofluorescence analyses confirmed the down-regulated expression of some of these genes, in particular of the cartilage oligomeric matrix protein and osteopontin, encoded by COMP and SPP1, respectively, and showed the predominant reduction and disassembly of the heparan sulfate specific GAGs, as well as of the PG perlecan and type III and V collagens. The key role of GalT-II in GAG synthesis and the crucial biological functions of PGs are consistent with the perturbation of many physiological functions that are critical for the correct architecture and homeostasis of various connective tissues, including skin, bone, cartilage, tendons, and ligaments, and generates the wide phenotypic spectrum of GalT-II-deficient patients.

An innovative route to activate silicon microcantilevers (MCs) for label free molecular recognition is presented. The method consists in coating the underivatized MCs with a functional ter-polymer based on N,N-dimethylacrylamide (DMA) bearing N-acryloyloxysuccinimide (NAS) and 3-(trimethoxysilyl)propyl-methacrylate (MAPS), two functional monomers that confer to the polymer the ability to react with nucleophilic species on biomolecules and with glass silanols, respectively. The polymer was deposited onto MCs by dip coating. Polymer coated MCs were tested in both static and dynamic modes of actuation, featuring detection of DNA hybridization as well as protein/protein interaction. In the dynamic experiments, focused on protein detection, the MCs showed an average mass responsivity of 0.4 Hz/pg for the first resonant mode and of 2.5 Hz/pg for the second resonant mode. The results of the static experiments, dedicated to DNA hybridization detection, allowed for direct estimation of the DNA duplex formation energetics, which resulted fully consistent with the nominal expected values. These results, together with easiness and cheapness, high versatility, and excellent stability of the recognition signal, make the presented route a reliable alternative to standard SAM functionalization (for microcantilevers (MCs) and for micro-electro-mechanical systems (MEMS) in general).

In this article we evaluated by atomic force microscopy (AFM) the effects of the (novel) tetrabranched antimicrobial peptide SB006 on morphology and mechanical properties of the gram-negative bacterium Pseudomonas aeruginosa. AFM imaging showed that SB006 causes the appearance of significant fragmentariness in the bacterial membrane and a severe volume decrease. Quantitative evaluation of the degree of fragmentariness was allowed by a new ad hoc image analysis procedure. The rigidity of the treated and untreated bacteria was measured through AFM tip nanoindentation measurements, and no differences registered. These results support the membrane interaction hypothesis, according to which SB006 targets the bacterial membranes and disrupts their permeability (allowing the leakage of cytoplasmic material and the subsequent shrinkage), but it does not affect the bacterium wall, which determines its rigidity.

Azospirillum brasilense glutamate synthase (GltS) is a complex iron-sulfur flavoprotein whose catalytically active alphabeta protomer (alpha subunit, 162kDa; beta subunit, 52.3 kDa) contains one FAD, one FMN, one [3Fe-4S](0,+1), and two [4Fe-4S](+1,+2) clusters. The structure of the alpha subunit has been determined providing information on the mechanism of ammonia transfer from L-glutamine to 2-oxoglutarate through a 30 A-long intramolecular tunnel. On the contrary, details of the electron transfer pathway from NADPH to the postulated 2-iminoglutarate intermediate through the enzyme flavin co-factors and [Fe-S] clusters are largely indirect. To identify the location and role of each one of the GltS [4Fe-4S] clusters, we individually substituted the four cysteinyl residues forming the first of two conserved C-rich regions at the N-terminus of GltS beta subunit with alanyl residues. The engineered genes encoding the beta subunit variants (and derivatives carrying C-terminal His6-tags) were co-expressed with the wild-type alpha subunit gene. In all cases the C/A substitutions prevented alpha and beta subunits association to yield the GltS alphabeta protomer. This result is consistent with the fact that these residues are responsible for the formation of glutamate synthase [4Fe-4S](+1,+2) clusters within the N-terminal region of the beta subunit, and that these clusters are implicated not only in electron transfer between the GltS flavins, but also in alphabeta heterodimer formation by structuring an N-terminal [Fe-S] beta subunit interface subdomain, as suggested by the three-dimensional structure of dihydropyrimidine dehydrogenase, an enzyme containing an N-terminal beta subunit-like domain.

A double coronary arteriovenous fistula (CAVF) was observed in a ten-year-old girl. A large, tortuous, and elongated right coronary artery, communicating with the right ventricle, was detected by two-dimensional echocardiography and confirmed at angiography. To our knowledge, no echocardiographic recognition of the origin and termination of a CAVF has been reported previously. Moreover, another fistula, connecting the left anterior descending coronary artery with the main pulmonary artery was also detected by selective left coronary arteriography. The anatomy of double CAVF was confirmed on surgery. A right CAVF draining into the right ventricle and a left CAVF draining into the main pulmonary artery seemed to be a very unusual combination.