Segregation, immunohistochemical, molecular and functional analyses classify a novel missense variant in fumarate hydratase (FH) as pathogenic.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome characterized by cutaneous leiomyomas, uterine leiomyomas, and aggressive renal cancer. Germline variants in the fumarate hydratase (FH) gene predispose to HLRCC. Identifying germline pathogenic FH variants enables lifetime renal cancer screening and genetic testing for family members. In this report, we present a FH missense variant (c.1039T>C (p.S347P)), initially classified as a variant of uncertain significance. Clinical assessment, histopathological findings, molecular genetic studies, and enzymatic activity studies support the re-classification of the FH c.1039T>C variant to "pathogenic" based on ACMG/AMP criteria. Further insights into pathological recognition of FH-deficient renal cancer are discussed and should be recognized. This study has shown how (a) detailed multi-disciplinary analyses of a single variant can reclassify rare missense variants in FH and (b) careful pathological review of renal cancers is obligatory when HLRCC is suspected.

Phenotypic, Technological, Safety, and Genomic Profiles of Gamma-Aminobutyric Acid-Producing Lactococcus lactis and Streptococcus thermophilus Strains Isolated from Cow's Milk.

Gamma-aminobutyric acid (GABA)-producing lactic acid bacteria (LAB) can be used as starters in the development of GABA-enriched functional fermented foods. In this work, four GABA-producing strains each of Lactococcus lactis and Streptococcus thermophilus species were isolated from cow's milk, and their phenotypic, technological, and safety profiles determined. Genome analysis provided genetic support for the majority of the analyzed traits, namely, GABA production, growth in milk, and the absence of genes of concern. The operon harboring the glutamate decarboxylase gene (gadB) was chromosomally encoded in all strains and showed the same gene content and gene order as those reported, respectively, for L. lactis and S. thermophilus. In the latter species, the operon was flanked (as in most strains of this species) by complete or truncated copies of insertion sequences (IS), suggesting recent acquisition through horizontal gene transfer. The genomes of three L. lactis and two S. thermophilus strains showed a gene encoding a caseinolytic proteinase (PrtP in L. lactis and PrtS in S. thermophilus). Of these, all but one grew in milk, forming a coagulum of good appearance and an appealing acidic flavor and taste. They also produced GABA in milk supplemented with monosodium glutamate. Two L. lactis strains were identified as belonging to the biovar. diacetylactis, utilized citrate from milk, and produced significant amounts of acetoin. None of the strains showed any noticeable antibiotic resistance, nor did their genomes harbor transferable antibiotic resistance genes or genes involved in toxicity, virulence, or pathogenicity. Altogether these results suggest that all eight strains may be considered candidates for use as starters or components of mixed LAB cultures for the manufacture of GABA-enriched fermented dairy products.

Transcriptional Profiling of Human Endothelial Cells Unveils PIEZO1 and Mechanosensitive Gene Regulation by Prooxidant and Inflammatory Inputs.

PIEZO1 is a mechanosensitive cation channel implicated in shear stress-mediated endothelial-dependent vasorelaxation. Since altered shear stress patterns induce a pro-inflammatory endothelial environment, we analyzed transcriptional profiles of human endothelial cells to determine the effect of altered shear stress patterns and subsequent prooxidant and inflammatory conditions on PIEZO1 and mechanosensitive-related genes (MRG). In silico analyses were validated in vitro by assessing PIEZO1 transcript levels in both the umbilical artery (HUAEC) and vein (HUVEC) endothelium. Transcriptional profiling showed that PIEZO1 and some MRG associated with the inflammatory response were upregulated in response to high (15 dyn/cm2) and extremely high shear stress (30 dyn/cm2) in HUVEC. Changes in PIEZO1 and inflammatory MRG were paralleled by p65 but not KLF or YAP1 transcription factors. Similarly, PIEZO1 transcript levels were upregulated by TNF-alpha (TNF-α) in diverse endothelial cell types, and pre-treatment with agents that prevent p65 translocation to the nucleus abolished PIEZO1 induction. ChIP-seq analysis revealed that p65 bonded to the PIEZO1 promoter region, an effect increased by the stimulation with TNF-α. Altogether this data showed that NF-kappa B activation via p65 signaling regulates PIEZO1 expression, providing a new molecular link for prooxidant and inflammatory responses and mechanosensitive pathways in the endothelium.

Divergence in Glyphosate Susceptibility between Steinchisma laxum Populations Involves a Pro106Ser Mutation.

The characterization of the mechanisms conferring resistance to herbicides in weeds is essential for developing effective management programs. This study was focused on characterizing the resistance level and the main mechanisms that confer resistance to glyphosate in a resistant (R) Steinchisma laxum population collected in a Colombian rice field in 2020. The R population exhibited 11.2 times higher resistance compared to a susceptible (S) population. Non-target site resistance (NTSR) mechanisms that reduced absorption and impaired translocation and glyphosate metabolism were not involved in the resistance to glyphosate in the R population. Evaluating the target site resistance mechanisms by means of enzymatic activity assays and EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene sequencing, the mutation Pro106Ser was found in R plants of S. laxum. These findings are crucial for managing the spread of S. laxum resistance in Colombia. To effectively control S. laxum in the future, it is imperative that farmers use herbicides with different mechanisms of action in addition to glyphosate and adopt Integrate Management Programs to control weeds in rice fields of the central valleys of Colombia.

Antioxidant, anti-inflammatory, hypoglycemic, and anti-hyperglycemic activity of chickpea protein hydrolysates evaluated in BALB-c mice.

Chickpea (ICC3761) protein hydrolysates have shown high in vitro antioxidant activity (AoxA) and antidiabetic potential. The aim of this study was to evaluate the in vivo activities (i.e., antioxidant, anti-inflammatory, hypoglycemic, and anti-hyperglycemic) of chickpea albumin hydrolysates (CAH) obtained with alcalase and pepsin-pancreatin (fractions ≤ 10 kDa). The CAH were analyzed for degree of hydrolysis (DH), electrophoretic and chromatographic profiles, and in vitro AoxA (2,2'-azino-bis(3-ethylbenzothiazolin)-6-sulfonic acid [ABTS], 2,2-diphenyl-1-pycrilhydrazyl [DPPH]). They were also evaluated for AoxA, anti-inflammatory and hypo- and anti-hyperglycemic activities in BALB-c mice. The DH was 20% for the alcalase CAH and 50% for the pepsin-pancreatin CAH, while the AoxA by ABTS (1 mg/mL) was 64.8% and 64.9% and by DPPH (5 mg/mL) was 48.0% and 31.1%. In the in vivo AoxA assay, mice of non-damaged control and those treated with both CAH showed similar alkaline phosphatase values, control and pepsin-pancreatin treated groups had similar malondialdehyde levels, while treated and non-damaged control groups had higher glutathione levels than the damaged control. Liver histopathology revealed that the pepsin-pancreatin CAH mitigated most of the pathological changes associated with the induced oxidative damage. Both CAH (2 mg/ear) reduced croton oil-induced ear edema in mice. The α-glucosidase inhibition of CAH (100 mg/mL) was 31.1% (alcalase) and 52.4% (pepsin-pancreatin). Mice treated with alcalase CAH (100 mg/mL) and glibenclamide exhibited similar hypoglycemic activities, whereas only those treated with the pepsin-pancreatin CAH (200 mg/kg body weight) showed anti-hyperglycemic activity. The results indicate that CAH can be used as a source of bioactive peptides with antioxidant, anti-inflammatory, hypoglycemic, and anti-hyperglycemic activities.

Transforaminal endoscopic lumbar discectomy: learning curve of a single surgeon.

Background: Transforaminal endoscopic lumbar discectomy (TELD) has well-recognized advantages and disadvantages in the literature. Some of the mentioned disadvantages are insufficient discectomy, higher recurrence rate and long learning curve (LC). The objective of this study is to describe the LC and analyze the survival rate of patients operated through TELD. Methods: Retrospective study of 41 cases operated through TELD by the same surgeon from June 2013 to January 2020, with a minimum follow-up of 6 months. Demographic data and information on operative time (OT), complications, hospital stay, hernia recurrence and reoperations were collected. LC of the TELD was analyzed using a cumulative sum (CUSUM) test for parameter stability for linear regression coefficients, using the CUSUM from recursive residuals. Results: Thirty-nine patients, 24 men (61.54%) and 15 women (38.46%), were included in the present cohort, and a total of 41 TELD were performed. The average OT was 96 minutes (SD =30) and the CUSUM of the recursive residuals shows learning of the TELD in the case 20. The mean OT in the first 20 cases was 114 minutes (SD =30) versus 80 minutes (SD =17) in the last 21 cases (P=0.0001). The rates of recurrent Dh were 17%, and 12% need reoperation. Conclusions: We consider that the LC of TELD requires operating 20 cases to perform the procedure with a significant reduction in OT, with minimal rates of reoperation and complications.

Broaden Research on Ocean Alkalinity Enhancement to Better Characterize Social Impacts.

Ocean alkalinity enhancement (OAE) is being considered as a way of achieving large-scale removals of carbon dioxide from the atmosphere. Research on the risks and benefits of different OAE approaches is expanding apace, but it remains difficult to anticipate and appraise the potential impacts to human communities that OAE might generate. These impacts, however, will be critical to evaluating the viability of specific OAE projects. This paper draws on the authors' involvement in interdisciplinary assessment of OAE (1) to identify the factors that currently limit characterization of potential social impacts and (2) to propose ways of reconfiguring OAE research to better consider these.

Convergent Adaptation of Multiple Herbicide Resistance to Auxin Mimics and ALS- and EPSPS-Inhibitors in Brassica rapa from North and South America.

Herbicide-resistant weeds have been identified and recorded on every continent where croplands are available. Despite the diversity of weed communities, it is of interest how selection has led to the same consequences in distant regions. Brassica rapa is a widespread naturalized weed that is found throughout temperate North and South America, and it is a frequent weed among winter cereal crops in Argentina and in Mexico. Broadleaf weed control is based on glyphosate that is used prior to sowing and sulfonylureas or mimic auxin herbicides that are used once the weeds have already emerged. This study was aimed at determining whether a convergent phenotypic adaptation to multiple herbicides had occurred in B. rapa populations from Mexico and Argentina by comparing the herbicide sensitivity to inhibitors of the acetolactate synthase (ALS), 5-enolpyruvylshikimate-3-phosphate (EPSPS), and auxin mimics. Five B. rapa populations were analyzed from seeds collected in wheat fields in Argentina (Ar1 and Ar2) and barley fields in Mexico (Mx1, Mx2 and MxS). Mx1, Mx2, and Ar1 populations presented multiple resistance to ALS- and EPSPS-inhibitors and to auxin mimics (2,4-D, MCPA, and fluroxypyr), while the Ar2 population showed resistance only to ALS-inhibitors and glyphosate. Resistance factors ranged from 947 to 4069 for tribenuron-methyl, from 1.5 to 9.4 for 2,4-D, and from 2.7 to 42 for glyphosate. These were consistent with ALS activity, ethylene production, and shikimate accumulation analyses in response to tribenuron-methyl, 2,4-D, and glyphosate, respectively. These results fully support the evolution of the multiple- and cross-herbicide resistance to glyphosate, ALS-inhibitors, and auxinic herbicides in B. rapa populations from Mexico and Argentina.

Spino-pelvic radiological parameters: Comparison of measurements obtained by radiologists using the traditional method versus spine surgeons using a semi-automated software (Surgimap).

Background: Spinopelvic balance measurement is a key point to get an appropriate diagnosis and treatment in a group of spine pathologies; thus, it seems necessary the evaluation of different methods for obtaining the most reliable values. For that reason, different automatic and semi-automatic computer-assisted tools have been developed, and one example of them is Surgimap. Purpose: To demonstrate that the sagittal balance measurements with Surgimap are equal and more time-efficient than with Agfa-Enterprise. Material and Methods: Retrospective-prospective study. Biased comparative analysis of radiographic measurements performed on two different occasions (96 h interval), between two spine surgeons using Surgimap and two radiologists using the traditional Cobb method (TCM) with the Agfa-Enterprise program in 36 full spine lateral X-ray, determining inter- and intra-observer reliability and the mean time required to obtain the measurements. Results: Measurements with both methods demonstrated an excellent intra-observer correlation (Surgimap: PCC 0.95 [0.85-0.99]; TCM: PCC 0.90 [0.81-0.99]). Inter-observer correlation also demonstrated an excellent relationship (PCC >0.95). Thoracic kyphosis (TK) demonstrated the lowest levels of inter-observer correlation (PCC: 0.75). The average time in seconds with TCM was 154.6, while with the Surgimap it was 41.8 s. Conclusion: Surgimap proved to be equally reliable and 3.5 times faster. Therefore, in consistency with the available literature, our results would allow us to promote the use of Surgimap as a clinical diagnostic tool considering precision and efficiency.

Reduced Glyphosate Movement and Mutation of the EPSPS Gene (Pro106Ser) Endow Resistance in Conyza canadensis Harvested in Mexico.

Glyphosate has been the most widely used herbicide for decades providing a unique tool, alone or in mixtures, to control weeds on citrus in Veracruz. Conyza canadensis has developed glyphosate resistance for the first time in Mexico. The level and mechanisms of resistance of four resistant populations Rs (R1, R2, R3, and R4) were studied and compared with that of a susceptible population (S). Resistance factor levels showed two moderately resistant populations (R2 and R3) and two highly resistant populations (R1 and R4). Glyphosate translocation through leaves to roots was ∼2.8 times higher in the S population than in the four R populations. A mutation (Pro106Ser) in the EPSPS2 gene was identified in the R1 and R4 populations. Mutation in the target site associated with reduced translocation is involved in increased glyphosate resistance in the R1 and R4 populations; whereas for the R2 and R3 populations, it was only mediated by reduced translocation. This is the first study of glyphosate resistance in C. canadensis from Mexico in which the resistance mechanisms involved are described in detail and control alternatives are proposed.

Optimized Route for the Fabrication of MnAlC Permanent Magnets by Arc Melting.

The rare-earth-free MnAlC alloy is currently considered a very promising candidate for permanent magnet applications due to its high anisotropy field and relatively high saturation magnetization and Curie temperature, besides being a low-cost material. In this work, we presented a simple fabrication route that allows for obtaining a magnetically enhanced bulk τ-MnAlC magnet. In the fabrication process, an electric arc-melting method was carried out to melt ingots of MnAlC alloys. A two-step solution treatment at 1200 °C and 1100 °C allowed us to synthesize a pure room-temperature ε-MnAlC ingot that completely transformed into τ-MnAlC alloy, free of secondary phases, after an annealing treatment at 550 °C for 30 min. The Rietveld refinements and magnetization measurements demonstrated that the quenched process produces a phase-segregated ε-MnAlC alloy that is formed by two types of ε-phases due to local fluctuation of the Mn. Room-temperature hysteresis loops showed that our improved τ-MnAlC alloy exhibited a remanent magnetization of 42 Am2/kg, a coercive field of 0.2 T and a maximum energy product, (BH)max, of 6.07 kJ/m3, which is higher than those reported in previous works using a similar preparation route. Experimental evidence demonstrated that the synthesis of a pure room-temperature ε-MnAlC played an important role in the suppression of undesirable phases that deteriorate the permanent magnet properties of the τ-MnAlC. Finally, magnetic images recorded by Lorentz microscopy allowed us to observe the microstructure and magnetic domain walls of the optimized τ-MnAlC. The presence of magnetic contrasts in all the observed grains allowed us to confirm the high-quality ferromagnetic behavior of the system.

Use of a rapid digital microfluidics-powered immunoassay for assessing measles and rubella infection and immunity in outbreak settings in the Democratic Republic of the Congo.

The Democratic Republic of the Congo (DRC) has a high measles incidence despite elimination efforts and has yet to introduce rubella vaccine. We evaluated the performance of a prototype rapid digital microfluidics powered (DMF) enzyme-linked immunoassay (ELISA) assessing measles and rubella infection, by testing for immunoglobulin M (IgM), and immunity from natural infection or vaccine, by testing immunoglobulin G (IgG), in outbreak settings. Field evaluations were conducted during September 2017, in Kinshasa province, DRC. Blood specimens were collected during an outbreak investigation of suspected measles cases and tested for measles and rubella IgM and IgG using the DMF-ELISA in the field. Simultaneously, a household serosurvey for measles and rubella IgG was conducted in a recently confirmed measles outbreak area. DMF-ELISA results were compared with reference ELISA results tested at DRC's National Public Health Laboratory and the US Centers for Disease Control and Prevention. Of 157 suspected measles cases, rubella IgM was detected in 54% while measles IgM was detected in 13%. Measles IgG-positive cases were higher among vaccinated persons (87%) than unvaccinated persons (72%). In the recent measles outbreak area, measles IgG seroprevalence was 93% overall, while rubella seroprevalence was lower for children (77%) than women (98%). Compared with reference ELISA, DMF-ELISA sensitivity and specificity were 82% and 78% for measles IgG; 88% and 89% for measles IgM; 85% and 85% for rubella IgG; and 81% and 83% for rubella IgM, respectively. Rubella infection was detected in more than half of persons meeting the suspected measles case definition during a presumed measles outbreak, suggesting substantial unrecognized rubella incidence, and highlighting the need for rubella vaccine introduction into the national schedule. The performance of the DMF-ELISA suggested that this technology can be used to develop rapid diagnostic tests for measles and rubella.

The drop plate method as an alternative for Azospirillum spp viable cell enumeration within the consensus protocol of the REDCAI network

Abstract Quality evaluation of commercial inoculants is essential to warrant an adequate cropresponse to inoculation within a biosecurity framework. In this sense, this work is aimed at standardizing and validating the drop plate method for the enumeration of Azospirillum viable cellsas an alternative to the spread plate technique, which is currently proposed in the consensusprotocol of the REDCAI network. Between 14 and 25 private and public laboratories partici-pated in three independent trials. We obtained consistent and robust results that allowed toconfirm that both techniques are equivalent, concluding that the drop plate method is an alternative enumeration technique that is adequate to be included in the abovementioned consensusprotocol.

Resumen La evaluación de la calidad de los inoculantes comerciales es fundamental para garantizar una adecuada respuesta de los cultivos a la inoculación dentro de un marco de bioseguridad. En este sentido, el objetivo de este trabajo fue la estandarización y validación de la técnica de la microgota para la cuantificación de Azospirillum como metodología alternativa a la técnica de siembra en superficie, propuesta actualmente en el protocolo consenso de la Red de Calidad de Inoculantes, REDCAI. Entre 14 y 25 laboratorios, tanto privados como públicos, participaron de tres ensayos independientes. A partir de ellos se obtuvieron resultados reproducibles y robustos que permiten confirmar que ambas técnicas son equivalentes y concluir que la técnica de recuento por la microgota es una alternativa adecuada para ser incluida dentro del mencionado protocolo consenso.

Experimental Enhancement of Feelings of Transcendence, Tenderness, and Expressiveness by Music in Christian Liturgical Spaces.

In western cultures, when it comes to places of worship and liturgies, music, acoustics and architecture go hand in hand. In the present study, we aimed to investigate whether the emotions evoked by music are enhanced by the acoustics of the space where the music was composed to be played on. We explored whether the emotional responses of western naïve listeners to two vocal pieces from the Renaissance, one liturgical and one secular, convolved with the impulse responses of four Christian temples from the United Kingdom, were modulated by the appropriate piece/space matching. In an alternative forced choice task where participants had to indicate their preference for the original recording of the piece (not convolved with any temple-like acoustics) vs. the convolved one, no significant differences were found. However, in the tasks where participants rated their emotional in response to each piece and acoustic condition, the factorial ANCOVA analyses performed on the results revealed significant effects. We observed that, across pieces and spaces, participants found the temple-like acoustics as more transcendent, compared to the acoustics of the original version of the pieces. In addition, they rated the secular piece as more tender and the liturgical piece as more expressive in its original versions, compared to the convolved ones. We conclude that the acoustic signature of the four Christian temples causes an exaltation of certain emotions on listeners, although this effect is not associated to one or another musical piece.

Metabolic changes associated with chilling injury tolerance in tomato fruit with hot water pretreatment.

Hot water treatment (HWT) of tomato (Solanum lycopersicum L.) fruit reduces the symptoms of chilling injury (CI). The aim of this study was to identify metabolites associated with HWT-induced CI tolerance in tomato fruit cv. Imperial. Mature green tomatoes with HWT (42°C/5 min) and control were stored under chilling conditions (5°C/20 days) and then ripened (21°C/7 days). Methanol extracts from pericarp were analyzed for total phenolics (TP), antioxidant activity (AoxA), and metabolic profiling by UPLC-DAD-MS and GC-MS. After cold storage and ripening, HWT fruit showed less CI, higher TP, and AoxA than control. It also showed an increased accumulation of phenolics, sugars, and some alkaloids that may be mediated by azelaic acid, glutamine, and tryptophan. The levels of N-feruloyl putrescine, esculeoside AII, and hydroxy-α-tomatine II were reduced. The better metabolic performance of HWT fruit under cold storage was associated with a higher accumulation of several metabolites (e.g., antioxidants and osmolytes) in ripening fruit. PRACTICAL APPLICATION: The identification of metabolites associated with the reduction of chilling injury (CI) symptoms in HWT tomato fruit extends the understanding of the mechanisms involved in CI tolerance. This information provides targets that could be used to develop strategies for preventing CI (e.g., genetic improvement of tomato, direct application of key metabolites). The application of such strategies will increase the economic value and decrease postharvest losses.

The drop plate method as an alternative for Azospirillum spp. viable cell enumeration within the consensus protocol of the REDCAI network.

Quality evaluation of commercial inoculants is essential to warrant an adequate crop response to inoculation within a biosecurity framework. In this sense, this work is aimed at standardizing and validating the drop plate method for the enumeration of Azospirillum viable cells as an alternative to the spread plate technique, which is currently proposed in the consensus protocol of the REDCAI network. Between 14 and 25 private and public laboratories participated in three independent trials. We obtained consistent and robust results that allowed to confirm that both techniques are equivalent, concluding that the drop plate method is an alternative enumeration technique that is adequate to be included in the abovementioned consensus protocol.

Non-Target-Site Resistance Mechanisms Endow Multiple Herbicide Resistance to Five Mechanisms of Action in Conyza bonariensis.

The repeated use of herbicides can lead to the selection of multiple resistance weeds. Some populations of Conyza bonariensis occurring in olive groves from southern Spain have developed resistance to various herbicides. This study determined the resistance levels to 2,4-D, glyphosate, diflufenican, paraquat, and tribenuron-methyl in a putative resistant (R) C. bonariensis population, and the possible non-target-site resistance (NTSR) mechanisms involved were characterized. Resistance factors varied as follows: glyphosate (8.9), 2,4-D (4.8), diflufenican (5.0), tribenuron-methyl (19.6), and paraquat (85.5). Absorption of 14C-glyphosate was up to 25% higher in the susceptible (S) population compared to the R one, but 14C-paraquat absorption was similar (up to 70%) in both populations. S plants translocated more than 60% of both 14C-glyphosate and 14C-paraquat toward shoots and roots, while R plants translocated less than 10%. The R population was able to metabolize 57% of the 2,4-D into nontoxic metabolites and 68% of the tribenuron-methyl into metsulfuron-methyl (10%), metsulfuron-methyl-hydroxylate (18%), and conjugate-metsulfuron-methyl (40%). Among the NTSR mechanisms investigated, absorption and translocation could be involved in glyphosate resistance, but only translocation for paraquat. Proofs of the presence of enhanced metabolism as a resistance mechanism were found for tribenuron-methyl and 2,4-D, but not for diflufenican. This research informs the first occurrence of multiple resistance to five herbicide classes (acetolactate synthase inhibitors, 5-enolpyruvylshikimate-3-phosphate synthase inhibitors, photosystem I electron diverters, photosystem II inhibitors, and synthetic auxin herbicides) in C. bonariensis.

Non-Target Site Mechanisms Endow Resistance to Glyphosate in Saltmarsh Aster (Aster squamatus).

Of the six-glyphosate resistant weed species reported in Mexico, five were found in citrus groves. Here, the glyphosate susceptibility level and resistance mechanisms were evaluated in saltmarsh aster (Aster squamatus), a weed that also occurs in Mexican citrus groves. The R population accumulated 4.5-fold less shikimic acid than S population. S plants hardly survived at 125 g ae ha-1 while most of the R plants that were treated with 1000 g ae ha-1, which suffered a strong growth arrest, showed a vigorous regrowth from the third week after treatment. Further, 5-enolpyruvylshikimate-3-phosphate basal and enzymatic activities did not diverge between populations, suggesting the absence of target-site resistance mechanisms. At 96 h after treatment, R plants absorbed ~18% less glyphosate and maintained 63% of the 14C-glyphsoate absorbed in the treated leaf in comparison to S plants. R plants metabolized twice as much (72%) glyphosate to amino methyl phosphonic acid and glyoxylate as the S plants. Three non-target mechanisms, reduced absorption and translocation and increased metabolism, confer glyphosate resistance saltmarsh aster. This is the first case of glyphosate resistance recorded for A. squamatus in the world.

Current gene panels account for nearly all homologous recombination repair-associated multiple-case breast cancer families.

It was hypothesized that variants in underexplored homologous recombination repair (HR) genes could explain unsolved multiple-case breast cancer (BC) families. We investigated HR deficiency (HRD)-associated mutational signatures and second hits in tumor DNA from familial BC cases. No candidates genes were associated with HRD in 38 probands previously tested negative with gene panels. We conclude it is unlikely that unknown HRD-associated genes explain a large fraction of unsolved familial BC.

Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9.

Despite their roles in intercellular communications, the different populations of extracellular vesicles (EVs) and their secretion mechanisms are not fully characterized: how and to what extent EVs form as intraluminal vesicles of endocytic compartments (exosomes), or at the plasma membrane (PM) (ectosomes) remains unclear. Here we follow intracellular trafficking of the EV markers CD9 and CD63 from the endoplasmic reticulum to their residency compartment, respectively PM and late endosomes. We observe transient co-localization at both places, before they finally segregate. CD9 and a mutant CD63 stabilized at the PM are more abundantly released in EVs than CD63. Thus, in HeLa cells, ectosomes are more prominent than exosomes. By comparative proteomic analysis and differential response to neutralization of endosomal pH, we identify a few surface proteins likely specific of either exosomes (LAMP1) or ectosomes (BSG, SLC3A2). Our work sets the path for molecular and functional discrimination of exosomes and small ectosomes in any cell type.