Increased expression of miR-320b in blood plasma of patients in response to SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recent research has demonstrated how epigenetic mechanisms regulate the host-virus interactions in COVID-19. It has also shown that microRNAs (miRNAs) are one of the three fundamental mechanisms of the epigenetic regulation of gene expression and play an important role in viral infections. A pilot study published by our research group identified, through next-generation sequencing (NGS), that miR-4433b-5p, miR-320b, and miR-16-2-3p are differentially expressed between patients with COVID-19 and controls. Thus, the objectives of this study were to validate the expression of these miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR) and to perform in silico analyses. Patients with COVID-19 (n = 90) and healthy volunteers (n = 40) were recruited. MiRNAs were extracted from plasma samples and validated using qRT-PCR. In addition, in silico analyses were performed using mirPath v.3 software. MiR-320b was the only miRNA upregulated in the case group com-pared to the control group. The in silico analyses indicated the role of miR-320b in the regulation of the KITLG gene and consequently in the inflammatory process. This study confirmed that miR-320b can distinguish patients with COVID-19 from control participants; however, further research is needed to determine whether this miRNA can be used as a target or a biomarker.

Sociodemographic and Lifestyle Characteristics Associated with Maternal Dietary Patterns in Mexico.

There is scarce evidence on sociodemographic and lifestyle characteristics that may explain adherence to different dietary patterns (DPs) during pregnancy. Our aims were to identify dietary patterns in a sample of pregnant Mexican women and to describe their association with selected sociodemographic and lifestyle characteristics. This is a secondary cross-sectional analysis of 252 mothers of children that participated as controls in a hospital-based case-control study of childhood leukemia. We obtained parents' information about selected sociodemographic characteristics, as well as alcohol and tobacco consumption. We also obtained dietary information during pregnancy. We identified DPs using cluster and factor analyses and we estimated their association with characteristics of interest. We identified two DPs using cluster analysis, which we called "Prudent" and "Non healthy", as well as three DPs through factor analysis, namely "Prudent", "Processed foods and fish", and "Chicken and vegetables". Characteristics associated with greater adherence to "Prudent" patterns were maternal education, older paternal age, not smoking, and being a government employee and/or uncovered population. Likewise, the "Processed foods and fish" pattern was associated with greater maternal and paternal education, as well as those with less household overcrowding. We did not identify sociodemographic variables related to the "Chicken and Vegetables" pattern. Our results may be useful to identify target populations that may benefit from interventions aimed to improve individual dietary decisions during pregnancy.

Exploring dietary differences among developmental stages of triatomines infected with Trypanosoma cruzi in different habitats.

Chagas disease affects millions of people in Colombia and worldwide, with its transmission influenced by ecological, environmental, and anthropogenic factors. There is a notable correlation between vector transmission cycles and the habitats of insect vectors of the parasite. However, the scale at which these cycles operate remains uncertain. While individual triatomine ecotopes such as palms provide conditions for isolated transmission cycles, recent studies examining triatomine blood sources in various habitats suggest a more intricate network of transmission cycles, linking wild ecotopes with human dwellings. This study aims to provide further evidence on the complexity of the scale of Trypanosoma cruzi transmission cycles, by exploring the different blood sources among developmental stages of infected triatomines in different habitats. We evaluated infection rates, parasite loads, feeding sources, and the distribution of Rhodnius prolixus insects in Attalea butyracea palms across three distinct habitats in Casanare, Colombia: peridomestics, pastures, and woodlands. Our results show that there is no clear independence in transmission cycles in each environment. Analyses of feeding sources suggest the movement of insects and mammals (primarily bats and didelphids) among habitats. A significant association was found between habitat and instar stages in collected R. prolixus. The N1 stage was correlated with pasture and woodland, while the N4 stage was related to pasture. Additionally, adult insects exhibited higher T. cruzi loads than N1, N2, and N3. We observed higher T. cruzi loads in insects captured in dwelling and pasture habitats, compared with those captured in woodland areas. Effective Chagas disease control strategies must consider the complexity of transmission cycles and the interplay between domestic and sylvatic populations of mammals and vectors.

Low-risk delisting strategy in highly sensitized patients without donor offers included in exchange donation programs. One single-center experience.

Donor exchange programs were designed to allocate organs for highly sensitized (HS) patients. The allocation algorithm differs slightly among countries and includes different strategies to improve access to transplants in HS patients. However, many HS patients with a calculated panel reactive of antibodies (cPRA) of 100 % remain on the waiting list for a long time. Some allocation algorithms assume immunological risk, including Imlifidase treatment, to increase the chance of transplantation in very HS patients. Here, we describe our unicenter experience of low-risk delisting strategy in 15 HS patients included in the Spanish donor exchange program without donor offers. After delisting, 7 out of 15 HS patients reduced the cPRA below 99.95 % and impacted the reduction of time on the waiting list (p = 0.01), where 5 out of 7 achieved transplantation. Within those HS that remained above 99.95 %, 1 out of 8 was transplanted. All the HS were transplanted with delisted DSA, and only one with DSA level rebounded early after transplantation. All HS transplanted after delisting maintain graft function. The transplant immunology laboratories are challenged to search intermediate risk assessment methods for delisting high HS patients.

Predicted deleterious variants in ABCA1, LPL, LPA and KIF6 are associated with statin response and adverse events in patients with familial hypercholesterolemia and disturb protein structure and stability.

OBJECTIVES: This study explored the association of deleterious variants in pharmacodynamics (PD) genes with statin response and adverse effects in patients with familial hypercholesterolemia (FH) and analyzed their potential effects on protein structure and stability. METHODS: Clinical and laboratory data were obtained from 144 adult FH patients treated with statins. A panel of 32 PD genes was analyzed by exon-targeted gene sequencing. Deleterious variants were identified using prediction algorithms and their structural effects were analyzed by molecular modeling studies. RESULTS: A total of 102 variants were predicted as deleterious (83 missense, 8 stop-gain, 4 frameshift, 1 indel, 6 splicing). The variants ABCA1 rs769705621 (indel), LPA rs41267807 (p.Tyr2023Cys) and KIF6 rs20455 (p.Trp719Arg) were associated with reduced low-density lipoprotein cholesterol (LDLc) response to statins, and the LPL rs1801177 (p.Asp36Asn) with increased LDLc response (P < 0.05). LPA rs3124784 (p.Arg2016Cys) was predicted to increase statin response (P = 0.022), and ABCA1 rs769705621 to increase the risk of statin-related adverse events (SRAE) (P = 0.027). LPA p.Arg2016Cys and LPL p.Asn36Asp maintained interactions with solvent, LPA p.Tyr2023Cys reduced intramolecular interaction with Gln1987, and KIF6 p.Trp719Arg did not affect intramolecular interactions. DDMut analysis showed that LPA p.Arg2016Cys and p.Tyr2023Cys and LPL p.Asp36Asn caused energetically favorable changes, and KIF6 p.Trp719Arg resulted in unfavorable energetic changes, affecting protein stability. CONCLUSION: Deleterious variants in ABCA1, LPA, LPL and KIF6 are associated with variability in LDLc response to statins, and ABCA1 rs769705621 is associated with SRAE risk in FH patients. Molecular modeling studies suggest that LPA p.Tyr2023Cys and KIF6 p.Trp719Arg disturb protein conformational structure and stability.

SARS-CoV-2 Mu variant in dogs visiting veterinary clinics during the third pandemic peak in Eastern Colombia.

The global presence of SARS-CoV-2 in household pets is acknowledged, yet documentation remains scarce, leaving many regions unexplored. Thus, our study sought to fill this gap by investigating SARS-CoV-2 presence in dogs visiting veterinary clinics during the third pandemic peak in eastern Colombia. We collected and analyzed 43 oropharyngeal and rectal swabs using real-time PCR assays targeting the Envelope Gene of SARS-CoV-2. Out of these, two dogs tested positive, indicating an infection rate of 4.7%. Further examination through complete sequencing and phylogenetic analysis revealed the lineage B.1.621 for the SARS-CoV-2 genome. Consequently, our study unveils the first documented cases of Canis lupus familiaris infected with the Mu variant of SARS-CoV-2, the variant with the most death burden during the whole pandemic in Colombia. Remarkably, these cases presented mild and reversible respiratory and gastrointestinal symptoms, or no clinical manifestations at all. This sheds light on the virus's interaction with our four-legged companions, offering valuable insights into its transmission dynamics and potential effects on animal health.

Optimizing perinatal wellbeing in pregnancy with obesity: a clinical trial with a multi-component nutrition intervention for prevention of gestational diabetes and infant growth and neurodevelopment impairment.

Pregnancy complicated by obesity represents an increased risk of unfavorable perinatal outcomes such as gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy, preterm birth, and impaired fetal growth, among others. Obesity is associated with deficiencies of micronutrients, and pregnant women with obesity may have higher needs. The intrauterine environment in pregnancies complicated with obesity is characterized by inflammation and oxidative stress, where maternal nutrition and metabolic status have significant influence and are critical in maternal health and in fetal programming of health in the offspring later in life. Comprehensive lifestyle interventions, including intensive nutrition care, are associated with a lower risk of adverse perinatal outcomes. Routine supplementation during pregnancy includes folic acid and iron; other nutrient supplementation is recommended for high-risk women or women in low-middle income countries. This study is an open label randomized clinical trial of parallel groups (UMIN Clinical Trials Registry: UMIN000052753, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000060194) to evaluate the effect of an intensive nutrition therapy and nutrient supplementation intervention (folic acid, iron, vitamin D, omega 3 fatty acids, myo-inositol and micronutrients) in pregnant women with obesity on the prevention of GDM, other perinatal outcomes, maternal and newborn nutritional status, and infant growth, adiposity, and neurodevelopment compared to usual care. Given the absence of established nutritional guidelines for managing obesity during pregnancy, there is a pressing need to develop and implement new nutritional programs to enhance perinatal outcomes.

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing.

Protein nanoparticles are effective platforms for antigen presentation and targeting effector immune cells in vaccine development. Encapsulins are a class of protein-based microbial nanocompartments that self-assemble into icosahedral structures with external diameters ranging from 24 to 42 nm. Encapsulins from Mxyococcus xanthus were designed to package bacterial RNA when produced in E. coli and were shown to have immunogenic and self-adjuvanting properties enhanced by this RNA. We genetically incorporated a 20-mer peptide derived from a mutant strain of the SARS-CoV-2 receptor binding domain (RBD) into the encapsulin protomeric coat protein for presentation on the exterior surface of the particle. This immunogen elicited conformationally-relevant humoral responses to the SARS-CoV-2 RBD. Immunological recognition was enhanced when the same peptide was presented in a heterologous prime/boost vaccination strategy using the engineered encapsulin and a previously reported variant of the PP7 virus-like particle, leading to the development of a selective antibody response against a SARS-CoV-2 RBD point mutant. While generating epitope-focused antibody responses is an interplay between inherent vaccine properties and B/T cells, here we demonstrate the use of orthogonal nanoparticles to fine-tune the control of epitope focusing.

The RoxyScan is a novel measurement of red blood cell deformability under oxidative and shear stress.

Exposure to both oxidative and shear stress, a condition that the red blood cell (RBC) continuously experiences in the circulation in vivo can be mimicked in a Couette type viscometer and monitored by ektacytometry. RBCs maintain their deformation and orientation under shear stress and oxidative stress until a threshold is reached at which these conditions appear to overwhelm the elaborate and complex pathways that maintain a proper redox environment in the cell. Oxidative stress under shear alters the ability of the cell to deform, changes cell morphology, its orientation in the shear stress field, and appears to alter intracellular and membrane characteristics. The application of the RoxyScan technology allows the comparison of oxidant effects and the role of antioxidant systems. This provides the opportunity to study the ability of RBC to deal with oxidative stress in various conditions, including RBC disorders such as sickle cell disease (SCD).

Single-nucleotide polymorphisms related to vitamin D metabolism and severity or mortality of COVID-19: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to verify the association between single-nucleotide polymorphisms (SNPs) in vitamin D-related genes and the severity or mortality of coronavirus disease 19 (COVID-19). We systematically searched PubMed, BVS/Bireme, Scopus, Embase, and Web of Science for relevant studies published until November 24, 2023. Twelve studies were included. Thirty-one SNPs related to four genes were studied (VDR, 13 SNPs; GC, 6 SNPs; DHCR7/NADSYN1, 6 SNPs; CYP2R1, 6 SNPs). Eight SNPs were examined in two or more studies (VDR rs731236, rs2228570, rs1544410, rs7975232, rs739837, rs757343, rs11568820, and rs4516035). Meta-analysis showed a significant association between the VDR rs1544410 Bb + bb genotype and b allele and an increased odds of developing severe/critical COVID-19 (Bb + bb vs. BB = 2 studies, OR = 1.73, 95% confidence interval (CI): 1.16-2.57, P = 0.007, I2 = 0%; b allele vs. B allele = 2 studies, OR = 1.31, 95% CI: 1.03-1.67; P = 0.03; I2 = 0%). Regarding the mortality rate, VDR rs731236 TT-genotype, TT + Tt genotype, and T allele; VDR rs1544410 bb-genotype, Bb + bb genotype, and b allele; VDR rs7975232 AA-genotype, AA + Aa genotype, and A allele; and VDR rs2228570 ff-genotype, Ff + ff genotype, and f allele were associated with increased odds of death due to COVID-19. In conclusion, the present study suggests that SNPs rs1544410 may serve as a predictive biomarker for COVID-19 severity and rs731236, rs1544410, rs7975232, and rs2228570 as predictive biomarkers for COVID-19 mortality. More well-designed studies involving a larger number of COVID-19 patients are required to validate and replicate these findings.

Scalp wound management: a narrative review from a neurosurgical perspective.

OBJECTIVE: This article aims to present a narrative review of current literature about the anatomical characteristics of the scalp as well as current practices in the management of surgical, traumatic and pressure injuries in the scalp, which are common in neurosurgery practice. METHOD: We searched PubMed for publications and book chapters in English from 2011 to 2021. We also included commonly referenced papers that we considered relevant to the subject with publication before these dates. We used the search terms 'laceration,' and/or 'neurosurgery' and/or, 'pressure injury,' and/or 'craniotomy,' and/or 'surgical incision' in combination with 'scalp,' and/or 'wound care.' We also searched the reference lists of publications identified by the search strategy and selected those that we judged relevant. RESULTS: We pre-selected 52 articles that covered various aspects of anatomy, pathophysiology, scalp wound management, or general wound care that we considered applied to the anatomical region of our interest. After abstract review, we selected 34 articles that met our search criteria and were included in our review. CONCLUSION: There is limited evidence regarding classification and care of scalp wounds. As a result, many of the current practices for scalp wound management are based on evidence derived from studies involving different anatomical regions, not considering its particular anatomy, vasculature and microbiome. Further research is needed for more comprehensive and effective protocols for the management of scalp injuries. However, this present review proposes responses to the identified gaps concerning the management of scalp wounds.

Transmission ecology of Trypanosoma cruzi by Rhodnius prolixus (Reduviidae: Triatominae) infesting palm-tree species in the Colombian Orinoco, indicates risks to human populations.

BACKGROUND: Chagas disease, affecting approximately eight million individuals in tropical regions, is primarily transmitted by vectors. Rhodnius prolixus, a triatomine vector, commonly inhabits in ecotopes with diverse palm tree species, creating optimal conditions for vector proliferation. This study aims to explore the transmission ecology of Trypanosoma cruzi, the causative parasite of Chagas disease, by investigating the feeding patterns and natural infection rates of R. prolixus specimens collected from various wild palm species in the Colombian Orinoco region. MATERIALS AND METHODS: To achieve this objective, we sampled 35 individuals from three palm species (Attalea butyracea, Acrocomia aculeata, and Mauritia flexuosa) in a riparian forest in the Casanare department of eastern Colombia, totaling 105 sampled palm trees. DNA was extracted and analyzed from 115 R. prolixus specimens at different developmental stages using quantitative PCR (qPCR) for T. cruzi detection and identification of discrete typing units. Feeding preferences were determined by sequencing the 12S rRNA gene amplicon through next-generation sequencing. RESULTS: A total of 676 R. prolixus specimens were collected from the sampled palms. The study revealed variation in population densities and developmental stages of R. prolixus among palm tree species, with higher densities observed in A. butyracea and lower densities in M. flexuosa. TcI was the exclusive T. cruzi discrete typing unit (DTU) found, with infection frequency positively correlated with R. prolixus abundance. Insects captured in A. butyracea exhibited higher abundance and infection rates than those from other palm species. The feeding sources comprised 13 mammal species, showing no significant differences between palm species in terms of blood sources. However, Didelphis marsupialis and Homo sapiens were present in all examined R. prolixus, and Dasypus novemcinctus was found in 89.47% of the insects. CONCLUSION: This study highlights the significance of wild palms, particularly A. butyracea, as a substantial risk factor for T. cruzi transmission to humans in these environments. High population densities and infection rates of R. prolixus were observed in each examined palm tree species.

Influence of dengue virus serotypes on the abundance of Aedes aegypti insect-specific viruses (ISVs).

A comprehensive understanding of the virome in mosquito vectors is crucial for assessing the potential transmission of viral agents, designing effective vector control strategies, and advancing our knowledge of insect-specific viruses (ISVs). In this study, we utilized Oxford Nanopore Technologies metagenomics to characterize the virome of Aedes aegypti mosquitoes collected in various regions of Colombia, a country hyperendemic for dengue virus (DENV). Analyses were conducted on groups of insects with previous natural DENV infection (DENV-1 and DENV-2 serotypes), as well as mosquito samples that tested negative for virus infection (DENV-negative). Our findings indicate that the Ae. aegypti virome exhibits a similar viral composition at the ISV family and species levels in both DENV-positive and DENV-negative samples across all study sites. However, differences were observed in the relative abundance of viral families such as Phenuiviridae, Partitiviridae, Flaviviridae, Rhabdoviridae, Picornaviridae, Bromoviridae, and Virgaviridae, depending on the serotype of DENV-1 and DENV-2. In addition, ISVs are frequently found in the core virome of Ae. aegypti, such as Phasi Charoen-like phasivirus (PCLV), which was the most prevalent and showed variable abundance in relation to the presence of specific DENV serotypes. Phylogenetic analyses of the L, M, and S segments of the PCLV genome are associated with sequences from different regions of the world but show close clustering with sequences from Brazil and Guadeloupe, indicating a shared evolutionary relationship. The profiling of the Ae. aegypti virome in Colombia presented here improves our understanding of viral diversity within mosquito vectors and provides information that opens the way to possible connections between ISVs and arboviruses. Future studies aimed at deepening our understanding of the mechanisms underlying the interactions between ISVs and DENV serotypes in Ae. aegypti could provide valuable information for the design of effective vector-borne viral disease control and prevention strategies.IMPORTANCEIn this study, we employed a metagenomic approach to characterize the virome of Aedes aegypti mosquitoes, with and without natural DENV infection, in several regions of Colombia. Our findings indicate that the mosquito virome is predominantly composed of insect-specific viruses (ISVs) and that infection with different DENV serotypes (DENV-1 and DENV-2) could lead to alterations in the relative abundance of viral families and species constituting the core virome in Aedes spp. The study also sheds light on the identification of the genome and evolutionary relationships of the Phasi Charoen-like phasivirus in Ae. aegypti in Colombia, a widespread ISV in areas with high DENV incidence.

Emergence of Dengue Virus Serotype 2 Cosmopolitan Genotype, Colombia.

Using Oxford Nanopore technologies and phylogenetic analyses, we sequenced and identified the cosmopolitan genotype of dengue virus serotype 2 isolated from 2 patients in the city of Villavicencio, Meta department, Colombia. This identification suggests the emergence of this genotype in the country, which warrants further surveillance to identify its epidemic potential.

An Outbreak of Acute Chagas Disease Possibly Spread through Oral Transmission Involving Animal Reservoirs in Eastern Colombia.

Chagas disease (CD) is a parasitic infection caused by the parasite Trypanosoma cruzi. Reports of CD cases associated with oral transmission have increased, particularly in Colombia, Brazil, and Venezuela. In this investigation, parasitological, serological, and molecular tests were conducted on samples obtained from humans, mammal reservoirs, and hosts involved in the assessment of a suspected oral transmission outbreak in Cubara, Boyaca, Colombia. Seropositivity was observed in 60% (3 of 5) of index patients and 6.4% (5 of 78) of close contacts. Trypanosoma cruzi DNA was detected by quantitative polymerase chain reaction in 100% of index cases, 6.4% (5 of 78) of close contacts, 60% (6 of 10) of canines, and 100% (5 of 5) of opossums. In all index cases, the TcI lineage was identified, along with two cases of mixed infection (TcI/TcII-TcVI). Hemoculture revealed a flagellate presence in 80% of opossums, whereas all triatomine bugs tested negative. Our findings suggest a potential oral transmission route through contamination with opossum secretions.

Characterizing viral species in mosquitoes (Culicidae) in the Colombian Orinoco: insights from a preliminary metagenomic study.

Mosquitoes (Diptera: Culicidae) are primary vectors of arthropod-borne viruses (arboviruses) that pose significant public health threats. Recent advances in sequencing technology emphasize the importance of understanding the arboviruses and insect-specific viruses (ISVs) hosted by mosquitoes, collectively called the "virome". Colombia, a tropical country with favorable conditions for the development and adaptation of multiple species of Culicidae, offers a favorable scenario for the transmission of epidemiologically important arboviruses. However, entomovirological surveillance studies are scarce in rural areas of the country, where humans, mosquitoes, and animals (both domestic and wild) coexist, leading to a higher risk of transmission of zoonotic diseases to humans. Thus, our study aimed to perform a preliminary metagenomic analysis of the mosquitoes of special relevance to public health belonging to the genera Ochlerotatus, Culex, Limatus, Mansonia, Psorophora, and Sabethes, within a rural savanna ecosystem in the Colombian Orinoco. We employed third-generation sequencing technology (Oxford Nanopore Technologies; ONT) to describe the virome of mosquitoes samples. Our results revealed that the virome was primarily shaped by insect-specific viruses (ISVs), with the Iflaviridae family being the most prevalent across all mosquito samples. Furthermore, we identified a group of ISVs that were common in all mosquito species tested, displaying the highest relative abundance concerning other groups of viruses. Notably, Hanko iflavirus-1 was especially prevalent in Culex eknomios (88.4%) and Ochlerotatus serratus (88.0%). Additionally, other ISVs, such as Guadalupe mosquito virus (GMV), Hubei mosquito virus1 (HMV1), Uxmal virus, Tanay virus, Cordoba virus, and Castlerea virus (all belonging to the Negevirus genus), were found as common viral species among the mosquitoes, although in lower proportions. These initial findings contribute to our understanding of ISVs within mosquito vectors of the Culicidae family in the Eastern Plains of Colombia. We recommend that future research explore deeper into ISV species shared among diverse vector species, and their potential interactions with arboviruses. In addition, we also showed the need for a thorough exploration of the influence of local rural habitat conditions on the shape of the virome in mosquito vectors.

Signal Transduction in an Enzymatic Photoreceptor Revealed by Cryo-Electron Microscopy.

Phytochromes are essential photoreceptor proteins in plants with homologs in bacteria and fungi that regulate a variety of important environmental responses. They display a reversible photocycle between two distinct states, the red-light absorbing Pr and the far-red light absorbing Pfr, each with its own structure. The reversible Pr to Pfr photoconversion requires covalently bound bilin chromophore and regulates the activity of a C-terminal enzymatic domain, which is usually a histidine kinase (HK). In plants, phytochromes translocate to nucleus where the C-terminal effector domain interacts with protein interaction factors (PIFs) to induce gene expression. In bacteria, the HK phosphorylates a response-regulator (RR) protein triggering downstream gene expression through a two-component signaling pathway. Although plant and bacterial phytochromes share similar structural composition, they have contrasting activity in the presence of light with most BphPs being active in the dark. The molecular mechanism that explains bacterial and plant phytochrome signaling has not been well understood due to limited structures of full-length phytochromes with enzymatic domain resolved at or near atomic resolution in both Pr and Pfr states. Here, we report the first Cryo-EM structures of a wild-type bacterial phytochrome with a HK enzymatic domain, determined in both Pr and Pfr states, between 3.75 and 4.13 Å resolution, respectively. Furthermore, we capture a distinct Pr/Pfr heterodimer of the same protein as potential signal transduction intermediate at 3.75 Å resolution. Our three Cryo-EM structures of the distinct signaling states of BphPs are further reinforced by Cryo-EM structures of the truncated PCM of the same protein determined for the Pr/Pfr heterodimer as well as Pfr state. These structures provide insight into the different light-signaling mechanisms that could explain how bacteria and plants see the light.

Maternal dietary patterns and acute leukemia in infants: results from a case control study in Mexico.

Background: Childhood cancer is the leading cause of disease-related mortality among children aged 5-14 years in Mexico, with acute leukemia being the most common cancer among infants. Examining the overall dietary patterns allows for a comprehensive assessment of food and nutrient consumption, providing a more predictive measure of disease risk than individual foods or nutrients. This study aims to evaluate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in Mexican infants. Methods: A hospital-based case-control study was conducted, comparing 109 confirmed acute leukemia cases with 152 age-matched controls. All participants (≤24 months) were identified at hospitals in Mexico City between 2010 and 2019. Data on a posteriori dietary patterns and other relevant variables were collected through structured interviews and dietary questionnaires. Multivariate logistic regression was employed to estimate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in infants. Results: The "Balanced & Vegetable-Rich" pattern, characterized by a balanced consumption of various food groups and higher vegetable intake, exhibited a negative association with acute leukemia when compared to the "High Dairy & Cereals" Pattern (adjusted odds ratio [OR] = 0.51; 95% confidence interval [CI]: 0.29, 0.90). We observed that mothers who gave birth to girls and adhered to a healthy dietary pattern during pregnancy exhibited significantly lower odds of their children developing AL compared to those who gave birth to boys [OR = 0.32 (95% CI 0.11, 0.97)]. Our results underscore the significance of maternal nutrition as a modifiable factor in disease prevention and the importance of prenatal health education.

Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a disorder of lipid metabolism that causes elevated low-density lipoprotein cholesterol (LDL-c) and increased premature atherosclerosis risk. Statins inhibit endogenous cholesterol biosynthesis, which reduces LDL-c plasma levels and prevent from cardiovascular events. This study aimed to explore the effects of statin treatment on serum lipidomic profile and to identify biomarkers of response in subjects with FH. Seventeen adult FH patients underwent a 6-week washout followed by 4-week treatment with atorvastatin (80 mg/day) or rosuvastatin (40 mg/day). LDL-c response was considered good (40-70 % reduction, n = 9) or poor (3-33 % reduction, n = 8). Serum lipidomic profile was analyzed by ultra-high-performance liquid chromatography combined with electrospray ionization tandem time-of-flight mass spectrometry, and data were analyzed using MetaboAnalyst v5.0. Lipidomic analysis identified 353 lipids grouped into 16 classes. Statin treatment reduced drastically 8 of 13 lipid classes, generating a characteristic lipidomic profile with a significant contribution of phosphatidylinositols (PI) 16:0/18:2, 18:0/18:1 and 18:0/18:2; and triacylglycerols (TAG) 18:2x2/18:3, 18:1/18:2/18:3, 16:1/18:2x2, 16:1/18:2/18:3 and 16:1/18:2/Arachidonic acid (p-adjusted <0.05). Biomarker analysis implemented in MetaboAnalyst subsequently identified PI 16:1/18:0, 16:0/18:2 and 18:0/18:2 as predictors of statin response with and receiver operating characteristic (ROC) areas under the curve of 0.98, 0.94 and 0.91, respectively. In conclusion, statins extensively modulate the overall serum lipid composition of FH individuals and these findings suggest that phosphatidyl-inositol molecules are potential predictive biomarkers of statin response.

Exploring the Landscape of the PP7 Virus-like Particle for Peptide Display.

Self-assembling virus-like particles (VLPs) can tolerate a wide degree of genetic and chemical manipulation to their capsid protein to display a foreign molecule polyvalently. We previously reported the successful incorporation of foreign peptide sequences in the junction loop and onto the C-terminus of PP7 dimer VLPs, as these regions are accessible for surface display on assembled capsids. Here, we report the implementation of a library-based approach to test the assembly tolerance of PP7 dimer capsid proteins to insertions or terminal extensions of randomized 15-mer peptide sequences. By performing two iterative rounds of assembly-based selection, we evaluated the degree of favorability of all 20 amino acids at each of the 15 randomized positions. Deep sequencing analysis revealed a distinct preference for the inclusion of hydrophilic peptides and negatively charged amino acids (Asp and Glu) and the exclusion of positively charged peptides and bulky and hydrophobic amino acid residues (Trp, Phe, Tyr, and Cys). Within the libraries tested here, we identified 4000 to 22,000 unique 15-mer peptide sequences that can successfully be displayed on the surface of the PP7 dimer capsid. Overall, the use of small initial libraries consisting of no more than a few million members yielded a significantly larger number of unique and assembly-competent VLP sequences than have been previously characterized for this class of nucleoprotein particle.