Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB.

Phase separation-based visualization of protein-protein interactions and kinase activities in plants.

Protein activities depend heavily on protein complex formation and dynamic posttranslational modifications, such as phosphorylation. The dynamic nature of protein complex formation and posttranslational modifications is notoriously difficult to monitor in planta at cellular resolution, often requiring extensive optimization. Here, we generated and exploited the SYnthetic Multivalency in PLants (SYMPL)-vector set to assay protein-protein interactions (PPIs) (separation of phases-based protein interaction reporter) and kinase activities (separation of phases-based activity reporter of kinase) in planta, based on phase separation. This technology enabled easy detection of inducible, binary and ternary PPIs among cytoplasmic and nuclear proteins in plant cells via a robust image-based readout. Moreover, we applied the SYMPL toolbox to develop an in vivo reporter for SNF1-related kinase 1 activity, allowing us to visualize tissue-specific, dynamic SnRK1 activity in stable transgenic Arabidopsis (Arabidopsis thaliana) plants. The SYMPL cloning toolbox provides a means to explore PPIs, phosphorylation, and other posttranslational modifications with unprecedented ease and sensitivity.

The U1 spliceosomal RNA is recurrently mutated in multiple cancers.

Cancers are caused by genomic alterations known as drivers. Hundreds of drivers in coding genes are known but, to date, only a handful of noncoding drivers have been discovered-despite intensive searching1,2. Attention has recently shifted to the role of altered RNA splicing in cancer; driver mutations that lead to transcriptome-wide aberrant splicing have been identified in multiple types of cancer, although these mutations have only been found in protein-coding splicing factors such as splicing factor 3b subunit 1 (SF3B1)3-6. By contrast, cancer-related alterations in the noncoding component of the spliceosome-a series of small nuclear RNAs (snRNAs)-have barely been studied, owing to the combined challenges of characterizing noncoding cancer drivers and the repetitive nature of snRNA genes1,7,8. Here we report a highly recurrent A>C somatic mutation at the third base of U1 snRNA in several types of tumour. The primary function of U1 snRNA is to recognize the 5' splice site via base-pairing. This mutation changes the preferential A-U base-pairing between U1 snRNA and the 5' splice site to C-G base-pairing, and thus creates novel splice junctions and alters the splicing pattern of multiple genes-including known drivers of cancer. Clinically, the A>C mutation is associated with heavy alcohol use in patients with hepatocellular carcinoma, and with the aggressive subtype of chronic lymphocytic leukaemia with unmutated immunoglobulin heavy-chain variable regions. The mutation in U1 snRNA also independently confers an adverse prognosis to patients with chronic lymphocytic leukaemia. Our study demonstrates a noncoding driver in spliceosomal RNAs, reveals a mechanism of aberrant splicing in cancer and may represent a new target for treatment. Our findings also suggest that driver discovery should be extended to a wider range of genomic regions.

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5' cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.

Insulin regulates neurovascular coupling through astrocytes.

Mice with insulin receptor (IR)-deficient astrocytes (GFAP-IR knockout [KO] mice) show blunted responses to insulin and reduced brain glucose uptake, whereas IR-deficient astrocytes show disturbed mitochondrial responses to glucose. While exploring the functional impact of disturbed mitochondrial function in astrocytes, we observed that GFAP-IR KO mice show uncoupling of brain blood flow with glucose uptake. Since IR-deficient astrocytes show higher levels of reactive oxidant species (ROS), this leads to stimulation of hypoxia-inducible factor-1α and, consequently, of the vascular endothelial growth factor angiogenic pathway. Indeed, GFAP-IR KO mice show disturbed brain vascularity and blood flow that is normalized by treatment with the antioxidant N-acetylcysteine (NAC). NAC ameliorated high ROS levels, normalized angiogenic signaling and mitochondrial function in IR-deficient astrocytes, and normalized neurovascular coupling in GFAP-IR KO mice. Our results indicate that by modulating glucose uptake and angiogenesis, insulin receptors in astrocytes participate in neurovascular coupling.

Dynamic GOLVEN-ROOT GROWTH FACTOR 1 INSENSITIVE signaling in the root cap mediates root gravitropism.

Throughout the exploration of the soil, roots interact with their environment and adapt to different conditions. Directional root growth is guided by asymmetric molecular patterns but how these become established or are dynamically regulated is poorly understood. Asymmetric gradients of the phytohormone auxin are established during root gravitropism, mainly through directional transport mediated by polarized auxin transporters. Upon gravistimulation, PIN-FORMED2 (PIN2) is differentially distributed and accumulates at the lower root side to facilitate asymmetric auxin transport up to the elongation zone where it inhibits cell elongation. GOLVEN (GLV) peptides function in gravitropism by affecting PIN2 abundance in epidermal cells. In addition, GLV signaling through ROOT GROWTH FACTOR 1 INSENSITIVE (RGI) receptors regulates root apical meristem maintenance. Here, we show that GLV-RGI signaling in these 2 processes in Arabidopsis (Arabidopsis thaliana) can be mapped to different cells in the root tip and that, in the case of gravitropism, it operates mainly in the lateral root cap (LRC) to maintain PIN2 levels at the plasma membrane (PM). Furthermore, we found that GLV signaling upregulates the phosphorylation level of PIN2 in an RGI-dependent manner. In addition, we demonstrated that the RGI5 receptor is asymmetrically distributed in the LRC and accumulates in the lower side of the LRC after gravistimulation. Asymmetric GLV-RGI signaling in the root cap likely accounts for differential PIN2 abundance at the PM to temporarily support auxin transport up to the elongation zone, thereby representing an additional level of control on the asymmetrical auxin flux to mediate differential growth of the root.

Genomic and phenotypic analysis of invasive Streptococcus suis isolated in Spain reveals genetic diversification and associated virulence traits.

Streptococcus suis is a zoonotic pathogen that causes a major health problem in the pig production industry worldwide. Spain is one of the largest pig producers in the world. This work aimed to investigate the genetic and phenotypic features of invasive S. suis isolates recovered in Spain. A panel of 156 clinical isolates recovered from 13 Autonomous Communities, representing the major pig producers, were analysed. MLST and serotyping analysis revealed that most isolates (61.6%) were assigned to ST1 (26.3%), ST123 (18.6%), ST29 (9.6%), and ST3 (7.1%). Interestingly, 34 new STs were identified, indicating the emergence of novel genetic lineages. Serotypes 9 (27.6%) and 1 (21.8%) prevailed, followed by serotypes 7 (12.8%) and 2 (12.2%). Analysis of 13 virulence-associated genes showed significant associations between ST, serotype, virulence patterns, and clinical features, evidencing particular virulence traits associated with genetic clusters. The pangenome was generated, and the core genome was distributed in 7 Bayesian groups where each group included a variable set of over- and under-represented genes of different categories. The study provides comprehensive data and knowledge to improve the design of new vaccines, antimicrobial treatments, and bacterial typing approaches.

Capacitive spectroscopy as transduction mechanism for wearable biosensors: opportunities and challenges.

Wearable sensors would revolutionize healthcare and personalized medicine by providing individuals with continuous and real-time data about their bodies and environments. Their integration into everyday life has the potential to enhance well-being, improve healthcare outcomes, and offer new opportunities for research. Capacitive sensors technology has great potential to enrich wearable devices, extending their use to more accurate physiological indicators. On the basis of capacitive sensors developed so far to monitor physical parameters, and taking into account the advances in capacitive biosensors, this work discusses the benefits of this type of transduction to design wearables for the monitoring of biomolecules. Moreover, it provides insights into the challenges that must be overcome to take advantage of capacitive transduction in wearable sensors for health.

The impact of reduced muscular fitness on cardiometabolic risk factors in children aged 9-11 years.

AIM: To analyse the relationships between muscular fitness (MF), fat mass (FM), fat-free mass (FFM) and its combined ratio with cardiometabolic risk (CMR) and whether the relationship between MF and CMR is mediated by body composition in schoolchildren. METHODS: A cross-sectional study was conducted on schoolchildren from Cuenca, Spain, between September and November 2017. FM and FFM were estimated using bioimpedance analysis. The CMR index was calculated from triglycerides-HDL-c ratio, arterial pressure and fasting insulin. The MF index was assessed using handgrip and standing long jump tests. Analysis of covariance models assessed CMR index differences across the MF index and the FM/FFM ratio categories. Mediation analysis examined whether the MF index and the CMR index association were mediated by FM, FFM or FM/FFM ratio. RESULTS: The analyses involved 485 schoolchildren aged 9-11 years (55.4% girls). Children with a higher MF index had a lower CMR index (p < 0.05). This association did not persist after controlling for FM/FFM. FM, FFM and FM/FFM ratio mediated the relationship between the MF index and the CMR index. CONCLUSION: Better levels of MF are associated with better cardiometabolic profile, but a healthy body composition is determinant to improve future health.

Climate change facilitated the early colonization of the Azores Archipelago during medieval times.

Humans have made such dramatic and permanent changes to Earth's landscapes that much of it is now substantially and irreversibly altered from its preanthropogenic state. Remote islands, until recently isolated from humans, offer insights into how these landscapes evolved in response to human-induced perturbations. However, little is known about when and how remote systems were colonized because archaeological data and historical records are scarce and incomplete. Here, we use a multiproxy approach to reconstruct the initial colonization and subsequent environmental impacts on the Azores Archipelago. Our reconstructions provide unambiguous evidence for widespread human disturbance of this archipelago starting between 700-60+50 and 850-60+60 Common Era (CE), ca. 700 y earlier than historical records suggest the onset of Portuguese settlement of the islands. Settlement proceeded in three phases, during which human pressure on the terrestrial and aquatic ecosystems grew steadily (i.e., through livestock introductions, logging, and fire), resulting in irreversible changes. Our climate models suggest that the initial colonization at the end of the early Middle Ages (500 to 900 CE) occurred in conjunction with anomalous northeasterly winds and warmer Northern Hemisphere temperatures. These climate conditions likely inhibited exploration from southern Europe and facilitated human settlers from the northeast Atlantic. These results are consistent with recent archaeological and genetic data suggesting that the Norse were most likely the earliest settlers on the islands.

End-of-life care needs in cancer patients: a qualitative study of patient and family experiences.

BACKGROUND: Cancer is a disease that transcends what is purely medical, profoundly affecting the day-to-day life of both patients and family members. Previous research has shown that the consequences of cancer are greatly aggravated in patients at the end of life, at a time when they must also grapple with numerous unmet needs. The main objective of this study was to obtain more in-depth insight into these needs, primarily in patients with end-stage cancer nearing death. METHODS: Semi-structured interviews were conducted in Spain with cancer patients at the end of life (n = 3) and their family members (n = 12). The findings from the interviews were analyzed using qualitative thematic analysis and a grounded theory approach. RESULTS: Four major themes emerged from the interviews that explored the needs and concerns of patients with cancer at the end of life: (1) physical well-being (2) emotional well-being (3) social well-being and (4), needs relating to information and autonomous decision-making. The interviews also shed light on the specific needs of family members during this period, namely the difficulties of managing increased caregiver burden and maintaining a healthy work-life balance. CONCLUSIONS: A lack of support, information and transparency during a period of immense vulnerability makes the end-of-life experience even more difficult for patients with cancer. Our findings highlight the importance of developing a more in-depth understanding of the needs of this population, so that informed efforts can be made to improve palliative healthcare and implement more comprehensive care and support at the end of life.

Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80-90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features. In this study, using a targeted next-generation sequencing (NGS) panel specifically designed for cHL research, we compared chemosensitive and chemorefractory diagnostic tissue samples of cHL patients. Furthermore, we longitudinally examined paired diagnosis-relapsesamples of chemorefractory cHL in order to define patterns of dynamic evolution and clonal selection. Pathogenic variants in NOTCH1 and NOTCH2 genes frequently arise in cHL. Mutations in genes associated with epigenetic regulation (CREBBP and EP300) are particularly frequent in relapsed/refractory cHL. The appearance of novel clones characterized by mutations previously not identified at diagnosis is a common feature in cHL cases showing chemoresistance to frontline treatments. Our results expand current molecular and pathogenic knowledge of cHL and support the performance of molecular studies in cHL prior to the initiation of first-line therapies.

Fulminant hepatitis due to spontaneous reactivation of virus B in an immunocompetent patient.

We present the case of a 52-year-old woman with a history of HBeAg-negative chronic hepatitis B virus (HBV) infection, viral load (VL) Z+<20,000U.l/ml with no evidence of liver fibrosis and, therefore, untreated. She presented to the emergency department with jaundice, epigastric pain, nausea, and vomiting. On admission, blood analysis revealed ALT 3982U/l, AST 3221U/l, Gamma-GT 80U/l, alkaline phosphatase 252U/l, LDH 960U/l, bilirrubin12.5mg/dl; no elevation of acute phase reactants, 141,000 platelets and coagulopathy with a prothrombin activity of 29%. Abdominal ultrasound showed no relevant findings. The serological profile revealed AgHBs+, anti-HBe+ y anti-HBc IgM+ and VL VHB>100 mills. Ul/ml, the remaining serology was negative and other causes of liver disease were ruled out. With the diagnosis of severe acute hepatitis (SAH) due to HBV reactivation (HBVR) treatment with entecavir was initiated. Given the analytical evolution (Table 1) and the appearance of encephalopathy grade I-II/IV, an urgent liver transplant was performed. The histological result of the explant was conclusive with intense interphase and lobular hepatitis with extensive areas of massive necrosis in both lobes, without hepatic fibrosis compatible with fulminant hepatitis (FH).

How different attributes are weighted in professionals' decision-making in Pediatric Dentistry-a protocol for guiding discrete choice experiment focused on shortening the evidence-based practice implementation for dental care.

BACKGROUND: Important evidence has been constantly produced and needs to be converted into practice. Professional consumption of such evidence may be a barrier to its implementation. Then, effective implementation of evidence-based interventions in clinical practice leans on the understanding of how professionals value attributes when choosing between options for dental care, permitting to guide this implementation process by maximizing strengthens and minimizing barriers related to that. METHODS: This is part of a broader project investigating the potential of incorporating scientific evidence into clinical practice and public policy recommendations and guidelines, identifying strengths and barriers in such an implementation process. The present research protocol comprises a Discrete Choice Experiment (DCE) from the Brazilian oral health professionals' perspective, aiming to assess how different factors are associated with professional decision-making in dental care, including the role of scientific evidence. Different choice sets will be developed, either focusing on understanding the role of scientific evidence in the professional decision-making process or on understanding specific attributes associated with different interventions recently tested in randomized clinical trials and available as newly produced scientific evidence to be used in clinical practice. DISCUSSION: Translating research into practice usually requires time and effort. Shortening this process may be useful for faster incorporation into clinical practice and beneficial to the population. Understanding the context and professionals' decision-making preferences is crucial to designing more effective implementation and/or educational initiatives. Ultimately, we expect to design an efficient implementation strategy that overcomes threats and potential opportunities identified during the DCEs, creating a customized structure for dental professionals. TRIAL REGISTRATION: https://osf.io/bhncv .

Enzyme-Linked DNA Displacement (ELIDIS) Assay for Ultrasensitive Electrochemical Detection of Antibodies.

Here we report the development of a method for the electrochemical ultrasensitive detection of antibodies that couples the programmability and versatility of DNA-based systems with the sensitivity provided by enzymatic amplification. The platform, termed Enzyme-Linked DNA Displacement (ELIDIS), is based on the use of antigen-DNA conjugates that, upon the bivalent binding of a specific target antibody, induce the release of an enzyme-DNA hybrid strand from a preformed duplex. Such enzyme-DNA hybrid strand can then be electrochemically detected with a disposable electrode with high sensitivity. We applied ELIDIS to demonstrate the sensitive (limit of detection in the picomolar range), specific and multiplexed detection of five different antibodies including three clinically relevant ones. ELIDIS is also rapid (it only requires two reaction steps), works well in complex media (serum) and is cost-effective. A direct comparison with a commercial ELISA kit for the detection of Cetuximab demonstrates the promising features of ELIDIS as a point-of-care platform for antibodies detection.

Mitochondrial dysfunction in chromaffin cells from the R6/1 mouse model of Huntington's disease: Impact on exocytosis and calcium current regulation.

From a pathogenic perspective, Huntington's disease (HD) is being considered as a synaptopathy. As such, alterations in brain neurotransmitter release occur. As the activity of the sympathoadrenal axis is centrally controlled, deficits in the exocytotic release of catecholamine release may also occur. In fact, in chromaffin cells (CCs) of the adrenal medulla of the R6/1 model of HD, decrease of secretion and altered kinetics of the exocytotic fusion pore have been reported. Those alterations could be linked to mitochondrial deficits occurring in peripheral CCs, similar to those described in brain mitochondria. Here we have inquired about alterations in mitochondrial structure and function and their impact on exocytosis and calcium channel currents (ICa). We have monitored various parameters linked to those events, in wild type (WT) and the R6/1 mouse model of HD at a pre-disease stage (2 months age, 2 m), and when motor deficits are present (7 months age, 7 m). In isolated CCs from 7 m and in the adrenal medulla of R6/1 mice, we found the following alterations (with respect 7 m WT mice): (i) augmented fragmented mitochondria and oxidative stress with increased oxidized glutathione; (ii) decreased basal and maximal respiration; (iii) diminution of ATP cell levels; (iv) mitochondrial depolarization; (v) drastic decrease of catecholamine release with poorer potentiation by protonophore FCCP; (vi) decreased ICa inhibition by FCCP; and (vii) lesser potentiation by BayK8644 of ICa and smaller prolongation of current deactivation. Of note was the fact several of these alterations were already manifested in CCs from 2 m R6/1 mice at pre-disease stages. Based on those results, a plausible hypothesis can be raised in the sense that altered mitochondrial function seems to be an early primary event in HD pathogenesis. This is in line with an increasing number of mitochondrial, metabolic, and inflammatory alterations being recently reported in various HD peripheral tissues.

Multicenter evaluation of BioFire JI panel related to improved microbiological diagnostics on acute osteoarticular infections.

Microbiological diagnosis of osteoarticular infections (OI) is crucial for a successful treatment. A prospective multicenter study including 262 synovial fluids with suspicion of acute OI was performed between July 2021 and October of 2022. BioFire Joint Infection Panel multiplex-PCR test was performed and results were compared with conventional cultures of synovial fluid specimens. In total, 136 microorganisms were detected, and fourteen samples were positive for more than one microorganism. In monomicrobial infections (n = 87) agreement with culture was 69%. In 26 samples, the multiplex PCR yield an additional positive result when culture result was negative. It helped in the detection of fastidious microorganisms as K. kingae and N. gonorrhoeae. This multiplex PCR has proven to be a useful technique that can be used for patients with high suspicion of acute OI in a rapid and automated manner.

Metabolomics analysis of human cumulus cells obtained from cumulus-oocyte complexes with different developmental potential.

STUDY QUESTION: Is the abundance of certain biochemical compounds in human cumulus cells (CCs) related to oocyte quality? SUMMARY ANSWER: Malonate, 5-oxyproline, and erythronate were positively associated with pregnancy potential. WHAT IS KNOWN ALREADY: CCs are removed and discarded prior to ICSI, thereby constituting an interesting biological material on which to perform molecular analysis aimed to predict oocyte developmental competence. Mitochondrial DNA content and transcriptional analyses in CC have been shown to provide a poor predictive value of oocyte competence, but the untargeted analysis of biochemical compounds (metabolomics) has been unexplored. STUDY DESIGN, SIZE, DURATION: CCs were obtained from three groups of cumulus-oocyte complexes (COCs) of known developmental potential: oocytes not developing to blastocyst following ICSI (Bl-); oocytes developing to blastocyst but failing to establish pregnancy following embryo transfer (P-); and oocytes developing to blastocyst able to establish a pregnancy (P+). Metabolomics analyses were performed on 12 samples per group, each sample comprising the CC recovered from a single COC. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human CC samples were obtained from IVF treatments. Only unfrozen oocytes and embryos not submitted to preimplantation genetic testing were included in the analysis. Metabolomics analysis was performed by ultra-high performance liquid chromatography-tandem mass spectroscopy. MAIN RESULTS AND THE ROLE OF CHANCE: The analysis identified 98 compounds, five of which were differentially abundant (P < 0.05) between groups: asparagine, proline, and malonate were less abundant in P- compared to Bl-, malonate and 5-oxoproline were less abundant in P- group compared to P+, and erythronate was less abundant in Bl- group compared to P+. No significant association between the abundance of the compounds identified and donor age or BMI was noted. LIMITATIONS, REASONS FOR CAUTION: Data dispersion and the lack of coherence between developmental groups preclude the direct use of metabolic markers in clinical practice, where the uterine environment plays a major role in pregnancy outcome. The abundance of other compounds not detected by the analysis may be associated with oocyte competence. As donors were lean (only two with BMI > 30 kg/m2) and young (<34 years old), a possible effect of obesity or advanced age on the CC metabolome could not be determined. WIDER IMPLICATIONS OF THE FINDINGS: The abundance of malonate, 5-oxyproline, and erythronate in CC was significantly higher in COCs ultimately establishing pregnancy, providing clues on the pathways required for oocyte competence. The untargeted analysis uncovered the presence of compounds that were not expected in CC, such as ß-citrylglutamate and the neurotransmitter N-acetyl-aspartyl-glutamate, which may play roles in chromatin remodeling and signaling, respectively. STUDY FUNDING/COMPETING INTEREST(S): Research was supported by the Industrial Doctorate Project IND2017/BIO-7748 funded by Madrid Region Government. The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.

GOLVEN peptides regulate lateral root spacing as part of a negative feedback loop on the establishment of auxin maxima.

Lateral root initiation requires the accumulation of auxin in lateral root founder cells, yielding a local auxin maximum. The positioning of auxin maxima along the primary root determines the density and spacing of lateral roots. The GOLVEN6 (GLV6) and GLV10 signaling peptides and their receptors have been established as regulators of lateral root spacing via their inhibitory effect on lateral root initiation in Arabidopsis. However, it was unclear how these GLV peptides interfere with auxin signaling or homeostasis. Here, we show that GLV6/10 signaling regulates the expression of a subset of auxin response genes, downstream of the canonical auxin signaling pathway, while simultaneously inhibiting the establishment of auxin maxima within xylem-pole pericycle cells that neighbor lateral root initiation sites. We present genetic evidence that this inhibitory effect relies on the activity of the PIN3 and PIN7 auxin export proteins. Furthermore, GLV6/10 peptide signaling was found to enhance PIN7 abundance in the plasma membranes of xylem-pole pericycle cells, which likely stimulates auxin efflux from these cells. Based on these findings, we propose a model in which the GLV6/10 signaling pathway serves as a negative feedback mechanism that contributes to the robust patterning of auxin maxima along the primary root.

Electrochemical ELASA: improving early cancer detection and monitoring.

The discovery of new molecular biomarkers of cancer during the last decades and the development of new diagnostic devices exploiting those have significantly contributed to the clinical analysis of cancer and to improve the outcomes. Among those, liquid biopsy sensors exploiting aptamers for the detection of cancer biomarkers in body fluids are useful and accurate tools for a fast and inexpensive non-invasive screening of population. The incorporation of aptamers in electrochemical sandwich biosensors using enzyme labels, a so-called ELASA, has demonstrated its utility to improve the detection schemes. In this review, we overview the existing ELASA assays for numerous cancer biomarkers as alternatives to the traditional ELISA and discuss their possibilities to reach the market, currently dominated by optical immunoassays.