Molecular Dynamic Simulations for Biopolymers with Biomedical Applications.

Computational modeling (CM) is a versatile scientific methodology used to examine the properties and behavior of complex systems, such as polymeric materials for biomedical bioengineering. CM has emerged as a primary tool for predicting, setting up, and interpreting experimental results. Integrating in silico and in vitro experiments accelerates scientific advancements, yielding quicker results at a reduced cost. While CM is a mature discipline, its use in biomedical engineering for biopolymer materials has only recently gained prominence. In biopolymer biomedical engineering, CM focuses on three key research areas: (A) Computer-aided design (CAD/CAM) utilizes specialized software to design and model biopolymers for various biomedical applications. This technology allows researchers to create precise three-dimensional models of biopolymers, taking into account their chemical, structural, and functional properties. These models can be used to enhance the structure of biopolymers and improve their effectiveness in specific medical applications. (B) Finite element analysis, a computational technique used to analyze and solve problems in engineering and physics. This approach divides the physical domain into small finite elements with simple geometric shapes. This computational technique enables the study and understanding of the mechanical and structural behavior of biopolymers in biomedical environments. (C) Molecular dynamics (MD) simulations involve using advanced computational techniques to study the behavior of biopolymers at the molecular and atomic levels. These simulations are fundamental for better understanding biological processes at the molecular level. Studying the wide-ranging uses of MD simulations in biopolymers involves examining the structural, functional, and evolutionary aspects of biomolecular systems over time. MD simulations solve Newton's equations of motion for all-atom systems, producing spatial trajectories for each atom. This provides valuable insights into properties such as water absorption on biopolymer surfaces and interactions with solid surfaces, which are crucial for assessing biomaterials. This review provides a comprehensive overview of the various applications of MD simulations in biopolymers. Additionally, it highlights the flexibility, robustness, and synergistic relationship between in silico and experimental techniques.

Assembly collapsing versus heterozygosity oversizing: detection of homokaryotic and heterokaryotic Laccaria trichodermophora strains by hybrid genome assembly.

Genome assembly and annotation using short-paired reads is challenging for eukaryotic organisms due to their large size, variable ploidy and large number of repetitive elements. However, the use of single-molecule long reads improves assembly quality (completeness and contiguity), but haplotype duplications still pose assembly challenges. To address the effect of read length on genome assembly quality, gene prediction and annotation, we compared genome assemblers and sequencing technologies with four strains of the ectomycorrhizal fungus Laccaria trichodermophora. By analysing the predicted repertoire of carbohydrate enzymes, we investigated the effects of assembly quality on functional inferences. Libraries were generated using three different sequencing platforms (Illumina Next-Seq, Mi-Seq and PacBio Sequel), and genomes were assembled using single and hybrid assemblies/libraries. Long reads or hybrid assemby resolved the collapsing of repeated regions, but the nuclear heterozygous versions remained unresolved. In dikaryotic fungi, each cell includes two nuclei and each nucleus has differences not only in allelic gene version but also in gene composition and synteny. These heterokaryotic cells produce fragmentation and size overestimation of the genome assembly of each nucleus. Hybrid assembly revealed a wider functional diversity of genomes. Here, several predicted oxidizing activities on glycosyl residues of oligosaccharides and several chitooligosaccharide acetylase activities would have passed unnoticed in short-read assemblies. Also, the size and fragmentation of the genome assembly, in combination with heterozygosity analysis, allowed us to distinguish homokaryotic and heterokaryotic strains isolated from L. trichodermophora fruit bodies.

Whole-genome sequence of Pseudomonas yamanorum OLsAu1 isolated from the edible wild ectomycorrhizal mushroom Lactarius sp. section Deliciosi.

We announce the genome sequencing, assembly, and annotation of the OLsAu1 strain and its taxonomic assignment to Pseudomonas yamanorum. The isolate comes from a wild edible ectomycorrhizal Lactarius sp. mushroom in the Abies forest. There is information regarding the strain's ability to promote plant growth, indicating its potential application in forestry.

Draft genome sequence of the highly copper-tolerant Methylobacterium radiotolerans MLP1 isolated from the rhizosphere of grasses adjacent to mine tailings.

We present the genome of a highly copper-tolerant pink-pigmented facultative methylotroph isolated from the rhizosphere of grasses growing close to mine tailings. Based on whole-genome taxonomic analyses, this isolate was named Methylobacterium radiotolerans MLP1. Studies are in progress to infer its genome-based copper resistome.

Functional annotation and comparative genomics analysis of Balamuthia mandrillaris reveals potential virulence-related genes.

Balamuthia mandrillaris is a pathogenic protozoan that causes a rare but almost always fatal infection of the central nervous system and, in some cases, cutaneous lesions. Currently, the genomic data for this free-living amoeba include the description of several complete mitochondrial genomes. In contrast, two complete genomes with draft quality are available in GenBank, but none of these have a functional annotation. In the present study, the complete genome of B. mandrillaris isolated from a freshwater artificial lagoon was sequenced and assembled, obtaining an assembled genome with better assembly quality parameter values than the currently available genomes. Afterward, the genome mentioned earlier, along with strains V039 and 2046, were subjected to functional annotation. Finally, comparative genomics analysis was performed, and it was found that homologous genes in the core genome potentially involved in the virulence of Acanthamoeba spp. and Trypanosoma cruzi. Moreover, eleven of fifteen genes were identified in the three strains described as potential target genes to develop new treatment approaches for B. mandrillaris infections. These results describe proteins in this protozoan's complete genome and help prioritize which target genes could be used to develop new treatments.

Effect of an Albumin Infusion Treatment Protocol on Delayed Cerebral Ischemia and Relevant Outcomes in Patients with Subarachnoid Hemorrhage.

BACKGROUND: An institutional management protocol for patients with subarachnoid hemorrhage (SAH) based on initial cardiac assessment, permissiveness of negative fluid balances, and use of a continuous albumin infusion as the main fluid therapy for the first 5 days of the intensive care unit (ICU) stay was implemented at our hospital in 2014. It aimed at achieving and maintaining euvolemia and hemodynamic stability to prevent ischemic events and complications in the ICU by reducing periods of hypovolemia or hemodynamic instability. This study aimed at assessing the effect of the implemented management protocol on the incidence of delayed cerebral ischemia (DCI), mortality, and other relevant outcomes in patients with SAH during ICU stay. METHODS: We conducted a quasi-experimental study with historical controls based on electronic medical records of adults with SAH admitted to the ICU at a tertiary care university hospital in Cali, Colombia. The patients treated between 2011 and 2014 were the control group, and those treated between 2014 and 2018 were the intervention group. We collected baseline clinical characteristics, cointerventions, occurrence of DCI, vital status after 6 months, neurological status after 6 months, hydroelectrolytic imbalances, and other SAH complication. Multivariable and sensitivity analyses that controlled for confounding and considered the presence of competing risks were used to adequately estimate the effects of the management protocol. The study was approved by our institutional ethics review board before study start. RESULTS: One hundred eighty-nine patients were included for analysis. The management protocol was associated with a reduced incidence of DCI (hazard ratio 0.52 [95% confidence interval 0.33-0.83] from multivariable subdistribution hazards model) and hyponatremia (relative risk 0.55 [95% confidence interval 0.37-0.80]). The management protocol was not associated with higher hospital or long-term mortality, nor with a higher occurrence of other unfavorable outcomes (pulmonary edema, rebleeding, hydrocephalus, hypernatremia, pneumonia). The intervention group also had lower daily and cumulative administered fluids compared with historic controls (p < 0.0001). CONCLUSIONS: A management protocol based on hemodynamically oriented fluid therapy in combination with a continuous albumin infusion as the main fluid during the first 5 days of the ICU stay appears beneficial for patients with SAH because it was associated with reduced incidence of DCI and hyponatremia. Proposed mechanisms include improved hemodynamic stability that allows euvolemia and reduces the risk of ischemia, among others.

Venom comparisons of endemic and micro-endemic speckled rattlesnakes Crotalus mitchellii, C. polisi and C. thalassoporus from Baja California Peninsula.

A high diversity of rattlesnake species can be found in the Baja California peninsula and the island of the Gulf of California, nevertheless, their venom has been poorly evaluated. The aim of this work was to present the first characterization of endemic Crotalus mitchellii, micro endemic C. polisi and C. thalassoporus venoms. All samples provoke human plasma coagulation showing doses in the rank of 2.3-41.0 µg and also produce rapid hydrolysis of the alpha chain of bovine fibrinogen while the beta chain is attacked at larger incubation periods by C. polisi and especially by C. thalassoporus. Phospholipase activity ranging from 23.2 to 173.8 U/mg. The venoms of C. thalassoporus and C. polisi show very high hemorrhagic activity (from 0.03 to 0.31 µg). A total of 130 toxin-related proteins were identified and classified into ten families. Crotalus mitchellii venom was characterized by high abundance of crotoxin-like and other phospholipase proteins (34.5%) and serine proteinases (29.8%). Crotalus polisi showed a similar proportion of metalloproteinases (34%) and serine proteinases (22.8%) components with important contribution of C-type lectins (14.3%) and CRiSP (14.0%) proteins. Venom of C. thalassoporus is dominated by metalloproteases that amount to more than 66% of total toxin proteins. These results provide a foundation for comprehending the biological, ecological and evolutionary significance of venom composition of speckled rattlesnake from the Baja California peninsula.

The inhibition of NCS-1 binding to Ric8a rescues fragile X syndrome mice model phenotypes.

Fragile X syndrome (FXS) is caused by the loss of function of Fragile X mental retardation protein (FMRP). FXS is one of the leading monogenic causes of intellectual disability (ID) and autism. Although it is caused by the failure of a single gene, FMRP that functions as an RNA binding protein affects a large number of genes secondarily. All these genes represent hundreds of potential targets and different mechanisms that account for multiple pathological features, thereby hampering the search for effective treatments. In this scenario, it seems desirable to reorient therapies toward more general approaches. Neuronal calcium sensor 1 (NCS-1), through its interaction with the guanine-exchange factor Ric8a, regulates the number of synapses and the probability of the release of a neurotransmitter, the two neuronal features that are altered in FXS and other neurodevelopmental disorders. Inhibitors of the NCS-1/Ric8a complex have been shown to be effective in restoring abnormally high synapse numbers as well as improving associative learning in FMRP mutant flies. Here, we demonstrate that phenothiazine FD44, an NCS-1/Ric8a inhibitor, has strong inhibition ability in situ and sufficient bioavailability in the mouse brain. More importantly, administration of FD44 to two different FXS mouse models restores well-known FXS phenotypes, such as hyperactivity, associative learning, aggressive behavior, stereotype, or impaired social approach. It has been suggested that dopamine (DA) may play a relevant role in the behavior and in neurodevelopmental disorders in general. We have measured DA and its metabolites in different brain regions, finding a higher metabolic rate in the limbic area, which is also restored with FD44 treatment. Therefore, in addition to confirming that the NCS-1/Ric8a complex is an excellent therapeutic target, we demonstrate the rescue effect of its inhibitor on the behavior of cognitive and autistic FXS mice and show DA metabolism as a FXS biochemical disease marker.

Probiotic Properties and Proteomic Analysis of Pediococcus pentosaceus 1101.

Pediococcus pentosaceus 1101 was identified by using 16S rRNA and MALDI-Biotyper. The strain was exposed to conditions that resemble the gastrointestinal tract (GT) to evaluate its probiotic properties. That included the growth kinetics, proteolytic and inhibitory activities within a pH range, survival at low pH and in the presence of bile salts, antagonistic activity, cell-adhesion properties, and antibiotic resistance. The evaluation was followed by a genomic and proteomic analysis that involved the identification of proteins obtained under control and gastrointestinal conditions. The strain showed antagonistic activity against Gram-negative and Gram-positive bacteria, high resistance to acidity (87% logarithmic survival rate, pH 2) and bile salts (99% logarithmic survival rate, 0.5% w/v), and hydrophobic binding, as well as sensitivity to penicillin, amoxicillin, and chloramphenicol. On the other hand, P. pentosaceus 1101 has a genome size of 1.76 Mbp, with 1754 coding sequences, 55 rRNAs, and 33 tRNAs. The proteomic analysis showed that 120 proteins were involved in mechanisms in which the strain senses the effects of acid and bile salts. Moreover, the strain produces at least one lytic enzyme (N-acetylmuramoyl-L-alanine amidase; 32 kDa) that may be related to the antimicrobial activity. Therefore, proteins identified might be a key factor when it comes to the adaptation of P. pentosaceus 1101 into the GT and associated with its technological and probiotic properties.

Aplicación de una ley matemática exponencial a la dinámica cardíaca en 16 horas: estudio realizado con 250 pacientes / Application of an exponential mathematical law to cardiac dynamics in 16 hours: a study of 250 patients

Resumen Introducción: Los sistemas dinámicos y la geometría fractal han sido el sustrato para el advenimiento de una ley matemática aplicada al diagnóstico de la dinámica cardíaca en 21 horas. Objetivo: Confirmar la aplicabilidad clínica de la ley matemática exponencial en 16 horas a partir de un estudio de concordancia diagnóstica frente a la norma de referencia. Materiales y método: Se realizó un estudio con 250 registros electrocardiográficos continuos y ambulatorios; 50 pertenecían a pacientes normales y 200 a pacientes con diversas enfermedades cardíacas. Se simuló la secuencia de frecuencias cardíacas y se construyeron los atractores correspondientes. Se calculó la dimensión fractal y la ocupación del atractor en el espacio generalizado de box-counting. Por último, se estableció el diagnóstico fisicomatemático en 16 y 21 horas y se efectuó la validación estadística. Resultados: Los espacios de ocupación para normalidad en la rejilla pequeña se encontraron entre 205 y 372, y entre 56 y 201 para dinámicas patológicas, lo cual permitió evidenciar la capacidad del método para diferenciar normalidad de enfermedad a través de la ocupación espacial de los atractores con base en la ley matemática en 16 horas. Se hallaron valores de sensibilidad y especificidad del 100% y un coeficiente kappa del orden de 1, luego de comparar el diagnóstico fisicomatemático frente a la norma de referencia. Conclusión: La ley matemática exponencial en 16 horas demostró su utilidad como herramienta de ayuda diagnóstica y predictiva, lo cual permitió diferenciar normalidad y estados evolutivos hacia enfermedad y agudización.

Abstract Introduction: Dynamic systems and fractal geometry have been the substrate for the rising of a mathematical law applied to the diagnosis of cardiac dynamics in 21 hours. Objective: To confirm the clinical applicability of the exponential mathematical law in 16 hours, with a study of diagnostic agreement against the Gold Standard. Materials and method: It was made a study with 250 ambulatory and continuous electrocardiographic recordings, 50 belonged to normal patients and 200 to patients with various cardiac pathologies. The sequence of heart rates was simulated, and attractors were constructed. It was calculated the fractal dimension of the attractor and its occupation in the generalized Box-Counting space. Finally, it was determined the physical-mathematical diagnostic in 16 and 21 hours, and statistical validation was performed. Results: The occupation spaces in the small grid were between 205 and 372 for normality, and between 56 and 201 for pathologic dynamics, which demonstrated the ability of the method to differentiate normal condition from sickness, through spatial occupation of attractors according to mathematical law in 16 hours. There were obtained values of sensitivity and specificity of 100% and Kappa coefficient was 1, after comparing the physic-mathematical analysis against the Gold Standard. Conclusion: The exponential mathematical law in 16 hours proved its utility as diagnostic and predictive tool support, allowing to differentiate normal, developmental stages to disease and exacerbation.

Molecular Detection and Characterization of Porcine Epidemic Diarrhea Virus and Porcine Aichivirus C Coinfection in México.

Swine enteric viral infections are responsible for substantial economic losses in the pork industry worldwide. Porcine epidemic diarrhea (PEDV) is one of the main causative agents of diarrhea in lactating pigs, and reports of PEDV coinfection with other enteric viruses highlight the importance of viral interactions for disease presentation and outcomes. Using next-generation sequencing (NGS) and sequence analyses from samples taken from piglets with acute diarrhea, we explored the possible interactions between PEDV and other less reported pathogens. PEDV coinfection with porcine kobuvirus (PKV) was detected in 36.4% (27/74) of samples. Full genomes from porcine coronavirus and kobuvirus were obtained, as was a partial porcine sapovirus genome (PSaV). The phylogenetic results show the clustering of these strains corresponding to the geographical relationship. To our knowledge, this is the first full genome and isolation report for porcine kobuvirus in México, as well as the first phylogenetic analysis for porcine sapovirus in the country. The NGS approach provides a better perspective of circulating viruses and other pathogens in affected production units.

Proteomic comparison of adult and juvenile Santa Catalina rattlesnake (Crotalus catalinensis) venom.

Rattlesnake's venom constitutes an important ecological trait that dynamically changes over time. Venoms of adult and juvenile rattleless rattlesnakes, Crotalus catalinensis, an endemic insular species from the Gulf of California, were compared by electrophoretic profile, fibrinogenolytic activity, and proteomic composition to assess ontogenetic variability. The SDS-PAGE profiles show important differences at 12, 22, and 45 kDa, which were prominent in adult samples and absent in juvenile samples, while bands around 20, 25, and 70 kDa are almost absent in adults. Both venoms hydrolyze Aa and Bb chains of fibrinogen generating different patterns of degradation products. This activity was partially inhibited by EDTA and PMSF and completely abolished only in the presence of both inhibitors. More than 260 proteins were identified and quantified in both venoms by proteomic analysis. Metalloproteinases (more than 60%), serine proteinases (14.5% in adult venom and 17.7% in juvenile venom), and C-type lectins (7.1 and 5.9%) represent the three most abundant toxin-related protein families. Bradykinin inhibitor peptides and L-amino acid oxidases were not detected in juvenile venom. A protein-specific comparison shows that adult and juvenile venom share about 30.5% of total toxin-related proteins, while 32% and 35% are exclusively present in adult and juvenile venoms, respectively. This work represents one of the first efforts to understand phenotypic diversity in the venom composition of insular rattlesnake species from Mexico.

Mortality in civilian trauma patients and massive blood transfusion treated with high vs low plasma: red blood cell ratio. Systematic review and meta-analysis / Mortalidad en pacientes con trauma civil y transfusion masiva tratados con una relación alta de plasma: globulos rojos versus una relacion baja. Revision sistemática y metaanálisis

Abstract Introduction: Massive bleeding in civilian trauma patients leads to dilutional coagulopathy. Transfusion with high plasma:red blood cell (RBC) ratio has been effective in reducing mortality in war trauma patients. However, in civilian trauma the evidence is controversial. Objective: To assess the impact on mortality of high vs low plasma:RBC ratio transfusion, in civilian trauma patients with massive bleeding. Methods: A systematic review and meta-analysis, including observational studies and clinical trials, was conducted. Data bases were systemically searched for relevant studies between January 2007 and June 2019. The main outcome was early (24-hours) and late (30-day) mortality. Fixed and random effects models were used. Results: Out of 1295 studies identified, 33 were selected: 2 clinical trials and 31 observational studies. The analysis of observational trials showed both decreased early mortality (odds ratio [OR] 0.67; 95% confidence interval [CI], 0.60-0.75) and late mortality (OR 0.79; 95% CI, 0.71-0.87) with the use of high plasma:RBC ratio transfusion, but there were no differences when clinical trials were evaluated (OR 0.89; 95% CI, 0.64-1.26). The exclusion of patients who died within the first 24 hours was a source of heterogeneity. The Injury Severity Score (ISS) altered the association between high plasma:RBC ratio and mortality, with a reduced protective effect when the ISS was high. Conclusion: The use of high vs low plasma: RBC ratio transfusion, in patients with massive bleeding due to civil trauma, has a protective effect on early and late mortality in observational studies. The exclusion of patients who died within the first 24 hours was a source of heterogeneity.

Resumen Introducción: El sangrado masivo en los pacientes con trauma civil propicia el desarrollo de coagulopatía dilucional. La transfusión de plasma y glóbulos rojos con una relación alta ha sido efectiva para disminuir la mortalidad en pacientes con trauma de guerra; sin embargo, su evidencia en trauma civil es controversial. Objetivo: Evaluar el efecto sobre la mortalidad de la transfusión de plasma: glóbulos rojos con relación alta (TPGR-RA) versus baja, en pacientes con sangrado masivo por trauma civil. Métodos: Se realizó una revisión sistemática y metaanálisis de estudios observacionales y experimentos clínicos publicados en el periodo de enero de 2007 a junio de 2019. El desenlace principal fue mortalidad temprana (24 horas) y tardía (30 días), utilizando el modelo de efectos fijos y aleatorios. Resultados: De 1.295 estudios identificados se incluyeron 33: dos experimentos clínicos y 31 estudios observacionales. El uso de TPGR-RA mostró una disminución de la mortalidad temprana (OR 0,67; IC 95 %, 0,60-0,75) y tardía (OR 0,79; IC 95 %, 0,71-0,87) cuando se analizaron los estudios observacionales, pero no hubo diferencias cuando se evaluaron los experimentos clínicos (OR 0,89; IC 95 %, 0,64-1,26). La exclusión de pacientes que fallecieron en las primeras 24 horas fue una fuente de heterogeneidad. La gravedad del trauma, ISS (por las iniciales en inglés de injury severity score)modificó la asociación entre la TPGR-RA y mortalidad, siendo menor el efecto protector cuando el ISS era alto. Conclusiones: El uso de TPGR-RA en pacientes con trauma civil y transfusión masiva (TM) tiene efecto protector sobre la mortalidad en los estudios observacionales. La exclusión de pacientes fallecidos en las primeras 24 horas fue causa de heterogeneidad.

New distribution records of subterranean crustaceans from cenotes in Yucatan (Mexico).

New records of 14 stygobiont crustacean species pertaining to six Malacostraca orders from 32 cenotes are presented, with their associated caves of the state of Yucatan, Mexico, together with an individual account for each species. Species composition of most of the investigated cenotes is examined for the first time. A thermosbaenacean and two amphipod species were not formally recorded to the cenote ecosystems of the state of Yucatan prior to our research. Distribution data of a cirolanid isopod previously known only from its type locality is also provided. Barcodes of mitochondrial cytochrome c oxidase subunit I for the reported peracarid species previously lacking this information have been included in present study as tools for species identification and a baseline of further molecular genetic analyses.

Draft Genome Sequences of Endophytic Isolates of Klebsiella variicola and Klebsiella pneumoniae Obtained from the Same Sugarcane Plant.

Endophytic Klebsiella variicola KvMx2 and Klebsiella pneumoniae KpMx1 isolates obtained from the same sugarcane stem were used for whole-genome sequencing. The genomes revealed clear differences in essential genes for plant growth, development, and detoxification, as well as nitrogen fixation, catalases, cellulases, and shared virulence factors described in the K. pneumoniae pathogen.

Draft Genome Sequence of Photorhabdus luminescens HIM3 Isolated from an Entomopathogenic Nematode in Agricultural Soils.

In this work, we report the draft genome sequence of Photorhabdus luminescens strain HIM3, a symbiotic bacterium associated with the entomopathogenic nematode Heterorhabditis indica MOR03, isolated from soil sugarcane in Yautepec, Morelos, Mexico. These bacteria have a G+C content of 42.6% and genome size of 5.47 Mb.

Draft Genome Sequence of a Pseudomonas aeruginosa NA04 Bacterium Isolated from an Entomopathogenic Nematode.

We report the draft genome sequence of Gram-negative bacterium Pseudomonas aeruginosa NA04, isolated from the entomopathogenic nematode Heterorhabditis indica MOR03. The draft genome consists of 54 contigs, a length of 6.37 Mb, and a G+C content 66.49%.

Draft Genome Sequence of Burkholderia cenocepacia Strain CEIB S5-2, a Methyl Parathion- and p-Nitrophenol-Degrading Bacterium, Isolated from Agricultural Soils in Morelos, Mexico.

Burkholderia cenocepacia is an opportunistic pathogen that belongs to Burkholderia cepacia complex (BCC). Burkholderia cenocepacia strain CEIB S5-2 was isolated from agricultural soils in Morelos, Mexico, and previously has shown its abilities for bioremediation. In this study, we report the draft genome sequence of Burkholderia cenocepacia strain CEIB S5-2.

Burkholderia cenocepacia Strain CEIB S5-1, a Rhizosphere-Inhabiting Bacterium with Potential in Bioremediation.

Burkholderia cenocepacia is considered an opportunistic pathogen from humans and may cause disease in plants. A bioprospection from a plaguicide-contaminated agricultural field in Mexico identified several methyl parathion-degrading bacteria. Here, we report the draft genome sequence of B. cenocepacia strain CEIB S5-1, which gave us clues into ecological biodiversity.

A Newly Sequenced Alcaligenes faecalis Strain: Implications for Novel Temporal Symbiotic Relationships.

We report here the draft genome sequence of Alcaligenes faecalis strain MOR02, a bacterium that is able to colonize nematodes in a temporary fashion and kill insects for their own benefit. The availability of the genome should enable us to explain these phenotypes.