Giantin mediates Golgi localization of Gal3-O-sulfotransferases and affects salivary mucin sulfation in Sjögren's disease patients.

Sjögren's disease is a chronic autoimmune disease characterized by symptoms of oral and ocular dryness and extra-glandular manifestations. Mouth dryness is not only due to reduced saliva volume but also to alterations in the quality of salivary mucins in these patients. Mucins play a leading role in mucosa hydration and protection, where sulfated and sialylated oligosaccharides retain water molecules at the epithelial surface. The correct localization of glycosyltransferases and sulfotransferases within the Golgi apparatus determines adequate O-glycosylation and sulfation of mucins, which depends on specific golgins that tether enzyme-bearing vesicles. Here, we show that a golgin called Giantin is mislocalized in salivary glands from patients with Sjögren's disease and forms protein complexes with Gal3-O-sulfotransferases (Gal3STs), which change their localization in Giantin knockout and knockdown cells. Our results suggest that Giantin could tether Gal3ST-bearing vesicles and that its altered localization could affect Gal3ST activity, explaining the decreased sulfation of MUC5B observed in salivary glands from patients with Sjögren's disease.

The complete mitochondrial genome of the endangered Atlantic Pygmy Devil Ray, Mobula hypostoma (Bancroft, 1831), from Brazil.

BACKGROUND: Mobulidae is a monophyletic family within the Myliobatiformes that comprises pelagic species represented by manta and devil rays. Among the genus Mobula, the Atlantic Pygmy Devil Ray - Mobula hypostoma - is reported in coastal regions exclusively in tropical and subtropical Atlantic Ocean from 1 to 100 m deep. In Brazil, M. hypostoma is one of the least studied Mobula species. It is regularly misidentified, especially as Mobula thurstoni, and is commonly listed as bycatch, in fishery inventories, or related to opportunistic sightings in the national territory. METHODS AND RESULTS: Here, we describe the complete nucleotide sequence of the mitochondrial genome (mitogenome) from Mobula hypostoma, which is 18,141 bp in length and comprises 13 protein-coding, two ribosomal RNA, and 22 transfer RNA genes. The M. hypostoma mitochondrial genes organisation and mitochondrial genome length are similar to other Mobula species, and the phylogenetic reconstruction indicates M. hypostoma as closely related to Mobula munkiana. CONCLUSIONS: The Brazilian mitogenome of M. hypostoma is expected to be a valuable resource for molecular-based species identification, and evolutionary and phylogeography studies.

Methods for multi-omic data integration in cancer research.

Multi-omics data integration is a term that refers to the process of combining and analyzing data from different omic experimental sources, such as genomics, transcriptomics, methylation assays, and microRNA sequencing, among others. Such data integration approaches have the potential to provide a more comprehensive functional understanding of biological systems and has numerous applications in areas such as disease diagnosis, prognosis and therapy. However, quantitative integration of multi-omic data is a complex task that requires the use of highly specialized methods and approaches. Here, we discuss a number of data integration methods that have been developed with multi-omics data in view, including statistical methods, machine learning approaches, and network-based approaches. We also discuss the challenges and limitations of such methods and provide examples of their applications in the literature. Overall, this review aims to provide an overview of the current state of the field and highlight potential directions for future research.

Oviposition biology, behavior, and avocado cultivar preferences of Heilipus lauri Boheman (Coleoptera: Curculionidae).

Heilipus lauri is a specialist avocado seed feeding weevil native to parts of México and is an invasive pest in Colombia. This weevil is considered an incursion risk because possible unintended introductions into areas outside of its native range can result in establishment, which threatens avocado production in invaded regions. Despite being a well-recognized pest of avocados, relatively little is known about oviposition biology, behavior, and cultivar preferences of this weevil. Field studies in commercial Hass avocado orchards in México and laboratory studies in a quarantine facility in California (USA) indicated that H. lauri prefers to oviposit into middle and bottom thirds of fruit. In the laboratory, an average of 1.7 eggs (range 1-6 eggs) are laid over a 24-h period in oviposition chambers by individual females. Conspecifics add eggs to these clutches, with up to 17 eggs being recorded in 1 oviposition chamber. This finding suggests that H. lauri does not use an oviposition deterring pheromone. Female weevils readily oviposit in artificial holes representing mechanical wounds on fruit. In comparison to the commercially dominant Hass variety, fruit from Lamb Hass and G22, a native Guatemalan variety, and to a lesser extent Gem, may be less preferred for oviposition when females have a choice of fruit in which to oviposit. Videography studies indicated that H. lauri exhibits predominantly diurnal activity with respect to oviposition behaviors, feeding, and walking.

Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications.

Tryptamines play diverse roles as neurotransmitters and psychoactive compounds found in various organisms. Psilocybin, a notable tryptamine, has garnered attention for its therapeutic potential in treating mental health disorders like depression and anxiety. Despite its promising applications, current extraction methods for psilocybin are labor-intensive and economically limiting. We suggest biocatalysis as a sustainable alternative, leveraging enzymes to synthesize psilocybin and other tryptamines efficiently. By elucidating psilocybin biosynthesis pathways, researchers aim to advance synthetic methodologies and industrial applications. This review underscores the transformative potential of biocatalysis in enhancing our understanding of tryptamine biosynthesis and facilitating the production of high-purity psilocybin and other tryptamines for therapeutic and research use.

Neither nectar nor deception: the role of floral rewards in the pollination system of Laelia (Orchidaceae: Laeliinae).

Orchids offer a variety of floral rewards to pollinators. In many orchid groups, however, the transfer of pollen is based on food-deception, as in the case of Laelia (including Schomburgkia s.s.), a genus assigned to the Neotropical subtribe Laeliinae. Here, we report on the reproductive biology of a Brazilian member of this subtribe, namely, Laelia gloriosa, occurring in the forested areas of southeastern Brazil. The study includes analyses of floral morphology, histochemistry, and the chemical analysis of floral rewards and scents. Pollinators and pollination mechanism data were collected in the field by means of focal observations. Analyses of breeding systems and the percentage of potentially viable seed were also recorded. The floral morphology of Laelia gloriosa indicates that this species is melittophilous. The flowers release a citrus-like fragrance that attracts many species of bee. The flowers offer waxy material as a reward, and this is collected exclusively by Meliponini bees. Several bee species visit the flowers. However, those of L. gloriosa are pollinated exclusively by Trigona spinipes. Pollinaria are deposited on the bee's scutellum. Plants of the studied population were entirely self-compatible, but pollinator-dependent. The frequency of visits to these flowers was greater than in rewardless Laeliinae. Our study provides the first evidence of lipoidal substances as a resource in Laeliinae. The discovery that an orchid species (Laelia gloriosa) of this subtribe, hitherto considered to be entirely pollinated by nectar-seeking pollinators, offers a floral waxy material and provides new insights into the evolution of this important subtribe.

Alzheimer's Disease Immunotherapy and Mimetic Peptide Design for Drug Development: Mutation Screening, Molecular Dynamics, and a Quantum Biochemistry Approach Focusing on Aducanumab::Aß2-7 Binding Affinity.

Seven treatments are approved for Alzheimer's disease, but five of them only relieve symptoms and do not alter the course of the disease. Aducanumab (Adu) and lecanemab are novel disease-modifying antiamyloid-ß (Aß) human monoclonal antibodies that specifically target the pathophysiology of Alzheimer's disease (AD) and were recently approved for its treatment. However, their administration is associated with serious side effects, and their use is limited to early stages of the disease. Therefore, drug discovery remains of great importance in AD research. To gain new insights into the development of novel drugs for Alzheimer's disease, a combination of techniques was employed, including mutation screening, molecular dynamics, and quantum biochemistry. These were used to outline the interfacial interactions of the Aducanumab::Aß2-7 complex. Our analysis identified critical stabilizing contacts, revealing up to 40% variation in the affinity of the Adu chains for Aß2-7 depending on the conformation outlined. Remarkably, two complementarity determining regions (CDRs) of the Adu heavy chain (HCDR3 and HCDR2) and one CDR of the Adu light chain (LCDR3) accounted for approximately 77% of the affinity of Adu for Aß2-7, confirming their critical role in epitope recognition. A single mutation, originally reported to have the potential to increase the affinity of Adu for Aß2-7, was shown to decrease its structural stability without increasing the overall binding affinity. Mimetic peptides that have the potential to inhibit Aß aggregation were designed by using computational outcomes. Our results support the use of these peptides as promising drugs with great potential as inhibitors of Aß aggregation.

Hot males: thermal biology of males and females during coercive mating in water striders Gerris lacustris.

Sexual conflict theory predicts that males that adopt coercive mating strategies impose costs to females during copulation. Nevertheless, conflicting mating strategies may also affect males, although such effects on males are often neglected in the literature. Here, we seek to understand whether male water striders (Gerris lacustris) experience higher body temperatures than females during coercive mating behavior. We we explored whether the water temperature affected male and female body temperature differently, considering that water contact by females might serve as a thermal regulator. We built generalized linear mixed models considering the male and female temperature as the dependent variables. Air temperature (as a proxy for solar radiation), water temperature, and sex were used as predictor variables. Our results suggest that males are warmer than females, and despite females coming into contact with water during skimming, this contact does not significantly contribute to lowering their body temperature or improving thermoregulation under the observed conditions. These findings provide novel insights into the thermal biology of water striders. Future studies should focus on addressing whether warmer temperatures confer some advantages to males, such as increased mobility and better ability to hold onto females or impose physiological constraints and fitness costs.

White matter structural bases for phase accuracy during tapping synchronization.

We determined the intersubject association between the rhythmic entrainment abilities of human subjects during a synchronization-continuation tapping task (SCT) and the macro- and microstructural properties of their superficial (SWM) and deep (DWM) white matter. Diffusion-weighted images were obtained from 32 subjects who performed the SCT with auditory or visual metronomes and five tempos ranging from 550 to 950 ms. We developed a method to determine the density of short-range fibers that run underneath the cortical mantle, interconnecting nearby cortical regions (U-fibers). Notably, individual differences in the density of U-fibers in the right audiomotor system were correlated with the degree of phase accuracy between the stimuli and taps across subjects. These correlations were specific to the synchronization epoch with auditory metronomes and tempos around 1.5 Hz. In addition, a significant association was found between phase accuracy and the density and bundle diameter of the corpus callosum (CC), forming an interval-selective map where short and long intervals were behaviorally correlated with the anterior and posterior portions of the CC. These findings suggest that the structural properties of the SWM and DWM in the audiomotor system support the tapping synchronization abilities of subjects, as cortical U-fiber density is linked to the preferred tapping tempo and the bundle properties of the CC define an interval-selective topography.

Two marine sulfur-reducing bacteria co-culture is essential for productive infection by a T4-like Escherichia coli-infecting phage.

The control of microbiologically influenced corrosion (MIC) challenges the oil exploration sector. The MIC results from electrochemical reactions facilitated by microorganisms such as sulfate-reducing bacteria (SRB), which adhere to the surface of the ducts forming biofilms. SRB uses sulfate as the final electron acceptor, resulting in hydrogen sulfide as the final product, a highly reactive corrosive, and toxic compound. Due to the high diversity of the SRB group, this study evaluated the effect of an Escherichia coli phage, with biofilm degrading enzymes, in preventing biofilm formation by microbial consortium P48SEP and reducing H2S production in a complex SRB community. Three phage concentrations were evaluated (104, 108 and 1012 UFP/ml). High and medium phage concentrations prevented biofilm development, as evidenced by scanning electron microscopy, chemical analysis, and cell counts. In addition, the virus altered the expression pattern of some bacterial genes and the relative abundance of proteins related to biofilm formation and cell stress response. Using a complex culture formed mainly by SRB, it was possible to observe the bacterial growth, H2S, and metabolic activity reduction after the phage was added. This study shows for the first time the ability of an E. coli-infecting phage to prevent the biofilm formation of an SRB consortium and infect and replicate at high concentrations on the non-specific host. This new finding turns the use of non-specific phages a promising alternative for the control of biocorrosion in oil and gas installations, on the other side, alert to the use of large concentration of phages and the influence on bacterial groups with geological importance, opening a research field in phage biology.

Arpin deficiency increases actomyosin contractility and vascular permeability.

Arpin was discovered as an inhibitor of the Arp2/3 complex localized at the lamellipodial tip of fibroblasts, where it regulated migration steering. Recently, we showed that arpin stabilizes the epithelial barrier in an Arp2/3-dependent manner. However, the expression and functions of arpin in endothelial cells (EC) have not yet been described. Arpin mRNA and protein are expressed in EC and downregulated by pro-inflammatory cytokines. Arpin depletion in Human Umbilical Vein Endothelial Cells causes the formation of actomyosin stress fibers leading to increased permeability in an Arp2/3-independent manner. Instead, inhibitors of ROCK1 and ZIPK, kinases involved in the generation of stress fibers, normalize the loss-of-arpin effects on actin filaments and permeability. Arpin-deficient mice are viable but show a characteristic vascular phenotype in the lung including edema, microhemorrhage, and vascular congestion, increased F-actin levels, and vascular permeability. Our data show that, apart from being an Arp2/3 inhibitor, arpin is also a regulator of actomyosin contractility and endothelial barrier integrity.

Remodeling of Uterine Tissues During Gestation of Potamotrygon wallacei (Elasmobranchii), a Neotropical Freshwater Stingray Endemic to the Negro River, Central Amazonia.

Neotropical freshwater stingrays of the subfamily Potamotrygoninae exhibit aplacental viviparity with uterine trophonemata. In this reproductive mode, females nourish and provide oxygenation to the embryo via the mucosa of the uterine wall. The aim of this study was to describe and histologically quantify the tissue components of the gravid uterus in an Amazonian freshwater stingray. Adult females of Potamotrygon wallacei were studied in different reproductive periods: resting stage, pregnant, and postpartum. During reproductive rest, the left ovary has numerous follicles compared to the right side. Therefore, uterine fertility is usually higher on the left side. The presence of an embryo in the right uterus suggests that the right ovary is also functional, although this only occurs in larger females. In females at reproductive rest, the wall of the uterus is formed by a mucosal layer (without the trophonemata) that contributes 16.7% to the thickness, while the myometrium accounts for 83.3% of the thickness. The mass-specific volume of the mucosal layer, inner circular, and outer longitudinal smooth muscle sheets tend to increase in the gravid uterus, indicating hypertrophy and hyperplasia of these components. During pregnancy, the trophonemata undergo marked tissue remodeling. Epithelial cells are organized into glandular acini and have apical secretory vesicles; furthermore, peripheral blood vessels proliferate and become dilated. These characteristics demonstrate that the gravid uterus of P. wallacei presents intense uterolactation activity and provides oxygenation to the fetus. Tissue remodeling occurs only in the uterus with the presence of an embryo. During postpartum, females have low body condition factor indicating a high reproductive cost. This study contributes to the knowledge of the reproductive biology of this species and will help us understand the impacts of climate change on the breeding areas of potamotrygonids.

Identification of novel broad host-range promoter sequences functional in diverse Pseudomonadota by a promoter-trap approach.

Finding novel promoter sequences is a cornerstone of synthetic biology. To contribute to the expanding catalog of biological parts, we employed a promoter-trap approach to identify novel sequences within an Antarctic microbial community that act as broad host-range promoters functional in diverse Pseudomonadota. Using Pseudomonas putida KT2440 as host, we generated a library comprising approximately 2,000 clones resulting in the identification of thirteen functional promoter sequences, thereby expanding the genetic toolkit available for this chassis. Some of the discovered promoter sequences prove to be broad host-range as they drove gene expression not only in P. putida KT2440 but also in Escherichia coli DH5α, Cupriavidus taiwanensis R1T, Paraburkholderia phymatum STM 815T, Ensifer meliloti 1021, and an indigenous Antarctic bacterium, Pseudomonas sp. UYIF39. Our findings enrich the existing catalog of biological parts, offering a repertoire of broad host-range promoter sequences that exhibit functionality across diverse members of the phylum Pseudomonadota, proving Antarctic microbial community as a valuable resource for prospecting new biological parts for synthetic biology.

Disentangling the Regulatory Response of Agrobacterium tumefaciens CHLDO to Glyphosate for Engineering Whole-Cell Phosphonate Biosensors.

Phosphonates (PHTs), organic compounds with a stable C-P bond, are widely distributed in nature. Glyphosate (GP), a synthetic PHT, is extensively used in agriculture and has been linked to various human health issues and environmental damage. Given the prevalence of GP, developing cost-effective, on-site methods for GP detection is key for assessing pollution and reducing exposure risks. We adopted Agrobacterium tumefaciens CHLDO, a natural GP degrader, as a host and the source of genetic parts for constructing PHT biosensors. In this bacterial species, the phn gene cluster, encoding the C-P lyase pathway, is regulated by the PhnF transcriptional repressor. We selected the phnG promoter, which displays a dose-dependent response to GP, to build a set of whole-cell biosensors. Through stepwise genetic optimization of the transcriptional cascade, we created a whole-cell biosensor capable of detecting GP in the 0.25-50 µM range in various samples, including soil and water.

Molecular analysis of cutaneous yeast isolates in the mycobiota of children with atopic dermatitis.

The skin of patients with atopic dermatitis (AD) has a greater diversity of mycobiota. An observational, prospective, cross-sectional, analytical, and comparative study was conducted involving 80 patients with AD Group (ADG) and 50 individuals without AD (wADG) in a tertiary hospital in Brazil. Skin scale samples were collected from the frontal, cervical, fossae cubital, and popliteal regions and identified using molecular biology techniques. The results showed that 47.5% of ADG had identified yeasts compared to 0% of wADG (P < .001). The yeasts Rhodotorula mucilaginosa and Candida parapsilosis were the most abundant. The probability of colonization increased with age, showing values of 40% at 60 months and 80% at 220 months (P = .09). The cervical region (12.5%) was colonized to the greatest extent. Our findings revealed that positive mycology was not more probable when the scoring of atopic dermatitis or eczema area and severity index value increased (P = .23 and .53, respectively). The results showed that the sex, age, and different population types directly affected the composition of the mycobiota in the population analyzed. A higher frequency of colonization and greater diversity of yeast species were detected in the cutaneous mycobiota of children with AD.

Atopic dermatitis (AD) is a skin disease that can be colonized by microorganisms. We evaluated patients with and without the disease and found a higher frequency of colonization by Rhodotorula mucilaginosa and Candida parapsilosis on the skin of children with AD.

Hedgehog components are overexpressed in a series of liver cancer cases.

Liver cancers, including hepatocellular carcinoma (HCC), are the sixth most common cancer and the third leading cause of cancer-related death worldwide, representing a global public health problem. This study evaluated nine patients with HCC. Six of the cases involved hepatic explants, and three involved hepatic segmentectomy for tumor resection. Eight out of nine tumors were HCC, with one being a combined hepatocellular-cholangiocarcinoma tumor. Conventional markers of hepatocellular differentiation (Hep Par-1, arginase, pCEA, and glutamine synthetase) were positive in all patients, while markers of hepatic precursor cells (CK19, CK7, EpCAM, and CD56) were negative in most patients, and when positive, they were detected in small, isolated foci. Based on in silico analysis of HCC tumors from The Cancer Genome Atlas database, we found that Hedgehog (HH) pathway components (GLI1, GLI2, GLI3 and GAS1) have high connectivity values (module membership > 0.7) and are strongly correlated with each other and with other genes in biologically relevant modules for HCC. We further validated this finding by analyzing the gene expression of HH components (PTCH1, GLI1, GLI2 and GLI3) in our samples through qPCR, as well as by immunohistochemical analysis. Additionally, we conducted a chemosensitivity analysis using primary HCC cultures treated with a panel of 18 drugs that affect the HH pathway and/or HCC. Most HCC samples were sensitive to sunitinib. Our results offer a comprehensive view of the molecular landscape of HCC, highlighting the significance of the HH pathway and providing insight into focused treatments for HCC.

Methoxy Chalcone Derivatives: Promising Antimicrobial Agents Against Phytopathogens.

Chalcone (E)-1,3-diphenyl-prop-2-en-1-one and a series of 14 methoxylated derivatives have been synthesized via Claisen-Schmidt aldol condensation and characterized by FTIR, CG/MS/DIC, 1D (1H and 13C), 2D (COSY, HSQC, and HMBC) NMR, and EMAR techniques. All molecules were tested at 1 mM concentration for antifungal (Sclerotium sp., Macrophomina phaesolina and Colletotrichum gloeosporioides), antibacterial (Acidovorax citrulli two strains), and antiprotozoal (Phytomonas serpens) activities. Unmodified chalcone (CH0) and derivatives CH1, CH2, CH8 stood out in terms of antifungal activity. CH0 presented IC50 values of 47.3 µM (9.8 µg/mL) for the fungus C. gloeosporioides. In addition, fluorescence microscopy indicated that CH0 promoted loss of hyphal cell membrane integrity. The CH1 and CH2 derivatives promoted the inhibition of Sclerotium sp. with IC50 of 127.5 µM (32.9 µg/mL) and 110.4 µM (29.6 µg/mL), respectively. All molecules showed high activity against the phytoparasite P. serpens with IC50 values of 0.98, 2.40, 10.25, and 3.11 µM for the derivatives CH2, CH3, CH5 and CH14 respectively. The results demonstrated that derivatives methoxylated in both rings (CH2) as well as derivatives with a furan ring associated with the methoxy group in ring A, as well as unmodified chalcone can be promising agricultural fungicides for controlling the fungi studied.

Personalized medicine: Clinical oncology on molecular view of treatment.

Cancer, the second leading global cause of death, impacts both physically and emotionally. Conventional treatments such as surgeries, chemotherapy, and radiotherapy have adverse effects, driving the need for more precise approaches. Precision medicine enables more targeted treatments. Genetic mapping, alongside other molecular biology approaches, identifies specific genes, contributing to accurate prognoses. The review addresses, in clinical use, a molecular perspective on treatment. Biomarkers like alpha-fetoprotein, beta-human chorionic gonadotropin, 5-hydroxyindoleacetic acid, programmed death-1, and cytotoxic T lymphocyte-associated protein 4 are explored, providing valuable information. Bioinformatics, with an emphasis on artificial intelligence, revolutionizes the analysis of biological data, offering more accurate diagnoses. Techniques like liquid biopsy are emphasized for early detection. Precision medicine guides therapeutic strategies based on the molecular characteristics of the tumor, as evidenced in the molecular subtypes of breast cancer. Classifications allow personalized treatments, highlighting the role of trastuzumab and endocrine therapies. Despite the benefits, challenges persist, including high costs, tumor heterogeneity, and ethical issues. Overcoming obstacles requires collaboration, ensuring that advances in molecular biology translate into accessible benefits for all.

Development of PCR-Multiplex Assays for Identification of the Herpotrichiellaceae Family and Agents Causing Chromoblastomycosis.

The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing chromoblastomycosis (CBM) and phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large Subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.