Psychophysiological Adaptations to Exercise Training in COVID-19 Patients: A Systematic Review.

Introduction: Many COVID-19 patients display adverse symptoms, such as reduced physical ability, poor quality of life, and impaired pulmonary function. Therefore, this systematic review is aimed at evaluating the effectiveness of physical exercise on various psychophysiological indicators among COVID-19 patients who may be at any stage of their illness (i.e., critically ill, hospitalized, postdischarge, and recovering). Methods: A systematic search was conducted in PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar from 2019 to 2021. Twenty-seven studies, which assessed a total of 1525 patients, were included and analysed. Results: Overall, data revealed significant improvements in the following parameters: physical function, dyspnoea, pulmonary function, quality of life (QOL), lower limb endurance and strength, anxiety, depression, physical activity level, muscle strength, oxygen saturation, fatigue, C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-α), lymphocyte, leukocytes, and a fibrin degradation product (D-dimer). Conclusions: Physical training turns out to be an effective therapy that minimises the severity of COVID-19 in the intervention group compared to the standard treatment. Therefore, physical training could be incorporated into conventional treatment of COVID-19 patients. More randomized controlled studies with follow-up evaluations are required to evaluate the long-term advantages of physical training. Future research is essential to establish the optimal exercise intensity level and assess the musculoskeletal fitness of recovered COVID-19 patients. This trial is registered with CRD42021283087.

Study protocol to examine the effects of acute exercise on motor learning and brain activity in children with developmental coordination disorder (ExLe-Brain-DCD).

INTRODUCTION: Developmental coordination disorder (DCD) is one of the most prevalent pediatric chronic conditions. Without proper intervention, significant delays in motor skill performance and learning may persist until adulthood. Moderate-to-vigorous physical exercise has been proven to improve motor learning (adaptation and consolidation) in children with or without disorders. However, the effect of a short bout of physical exercise on motor adaptation and consolidation in children with DCD has not been examined. Furthermore, the role of perceptual-motor integration and attention as mediators of learning has not been examined via neuroimaging in this population. OBJECTIVES: Therefore, the primary aims of this project will be to compare children with and without DCD to (a) examine the effect of acute exercise on motor learning (adaptation and consolidation) while performing a rotational visuo-motor adaptation task (rVMA), and (b) explore cortical activation in the dorsolateral- and ventrolateral-prefrontal cortex areas while learning the rVMA task under rest or post-exercise conditions. METHODS: One hundred twenty children will be recruited (60 DCD, 60 controls) and within-cohort randomly assigned to either exercise (13-minute shuttle run task) or rest prior to performing the rVMA task. Adaptation and consolidation will be evaluated via two error variables and three retention tests (1h, 24h and 7 days post adaptation). Cortical activation will be registered via functional near-infrared spectroscopy (fNIRS) during the baseline, adaptation, and consolidation. DISCUSSION: We expect to find exercise benefits on motor learning and attention so that children with DCD profiles will be closer to those of children with typical development. The results of this project will provide further evidence to: (a) better characterize children with DCD for the design of educational materials, and (b) establish acute exercise as a potential intervention to improve motor learning and attention.

Salivary Protein Cyclin-Dependent Kinase-like from Grain Aphid Sitobion avenae Suppresses Wheat Defense Response and Enhances Aphid Adaptation.

Aphids are insect pests that suck phloem sap and introduce salivary proteins into plant tissues through saliva secretion. The effector of salivary proteins plays a key role in the modulation of host plant defense responses and enhancing aphid host adaptation. Based on previous transcriptome sequencing results, a candidate effector cyclin-dependent kinase-like (CDK) was identified from the grain aphid Sitobion avenae. In this study, the function of SaCDK in wheat defense response and the adaptation of S. avenae was investigated. Our results showed that the transient overexpression of SaCDK in tobacco Nicotiana benthamiana suppressed cell death triggered by mouse pro-apoptotic protein-BAX or Phytophthora infestans PAMP-INF1. SaCDK, delivered into wheat cells through a Pseudomonas fluorescens-mediated bacterial type III secretion system, suppressed callose deposition in wheat seedlings, and the overexpression of SaCDK in wheat significantly decreased the expression levels of salicylic acid and jasmonic acid signaling pathway-related genes phenylalanine ammonia lyase (PAL), pathogenesis-related 1 protein (PR1), lipoxygenase (LOX) and Ω-3 fatty acid desaturase (FAD). In addition, aphid bioassay results showed that the survival and fecundity of S. avenae were significantly increased while feeding on the wheat plants carrying SaCDK. Taken together, our findings demonstrate that the salivary protein SaCDK is involved in inhibiting host defense response and improving its host adaptation, which lays the foundation to uncover the mechanism of the interaction of cereal aphids and host plants.

The Impact of Normobaric Hypoxia and Intermittent Hypoxic Training on Cardiac Biomarkers in Endurance Athletes: A Pilot Study.

This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the myocardium during acute exercise and altitude/hypoxic training remains less understood. We aimed to determine how a single bout of intense interval exercise and a four-week period of high-intensity endurance training under normobaric hypoxia affect cardiac marker activity in swimmers. Sixteen young male swimmers were divided into two groups: one undergoing training in hypoxia and the other in normoxia. Cardiac markers, including troponin I and T (cTnI and cTnT), heart-type fatty acid-binding protein (H-FABP), creatine kinase-MB isoenzyme (CK-MB), and myoglobin (Mb), were analyzed to assess the myocardium's response. We found no significant differences in the physiological response of the cardiac muscle to intense physical exertion between hypoxia and normoxia. Four weeks of IHT did not alter the resting levels of cTnT, cTnI, and H-FABP, but it resulted in a noteworthy decrease in the resting concentration of CK-MB, suggesting enhanced cardiac muscle adaptation to exercise. In contrast, a reduction in resting Mb levels was observed in the control group training in normoxia. These findings suggest that IHT at moderate altitudes does not adversely affect cardiac muscle condition and may support cardiac muscle adaptation, affirming the safety and efficacy of IHT as a training method for athletes.

Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation.

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.

The tetraploid wheat (Triticum dicoccum (Schrank) Schuebl.) improves nitrogen uptake and assimilation adaptation to nitrogen-deficit stress.

MAIN CONCLUSION: The genetic diversity in tetraploid wheat provides a genetic pool for improving wheat productivity and environmental resilience. The tetraploid wheat had strong N uptake, translocation, and assimilation capacity under N deficit stress, thus alleviating growth inhibition and plant N loss to maintain healthy development and adapt to environments with low N inputs. Tetraploid wheat with a rich genetic variability provides an indispensable genetic pool for improving wheat yield. Mining the physiological mechanisms of tetraploid wheat in response to nitrogen (N) deficit stress is important for low-N-tolerant wheat breeding. In this study, we selected emmer wheat (Kronos, tetraploid), Yangmai 25 (YM25, hexaploid), and Chinese spring (CS, hexaploid) as materials. We investigated the differences in the response of root morphology, leaf and root N accumulation, N uptake, translocation, and assimilation-related enzymes and gene expression in wheat seedlings of different ploidy under N deficit stress through hydroponic experiments. The tetraploid wheat (Kronos) had stronger adaptability to N deficit stress than the hexaploid wheats (YM25, CS). Kronos had better root growth under low N stress, expanding the N uptake area and enhancing N uptake to maintain higher NO3- and soluble protein contents. Kronos exhibited high TaNRT1.1, TaNRT2.1, and TaNRT2.2 expression in roots, which promoted NO3- uptake, and high TaNRT1.5 and TaNRT1.8 expression in roots and leaves enhanced NO3- translocation to the aboveground. NR and GS activity in roots and leaves of Kronos was higher by increasing the expression of TANIA2, TAGS1, and TAGS2, which enhanced the reduction and assimilation of NO3- as well as the re-assimilation of photorespiratory-released NH4+. Overall, Kronos had strong N uptake, translocation, and assimilation capacity under N deficit stress, alleviating growth inhibition and plant N loss and thus maintaining a healthy development. This study reveals the physiological mechanisms of tetraploid wheat that improve nitrogen uptake and assimilation adaptation under low N stress, which will provide indispensable germplasm resources for elite low-N-tolerant wheat improvement and breeding.

Tissue adaptation of CD4 T lymphocytes in homeostasis and cancer.

The immune system is traditionally classified as a defense system that can discriminate between self and non-self or dangerous and non-dangerous situations, unleashing a tolerogenic reaction or immune response. These activities are mainly coordinated by the interaction between innate and adaptive cells that act together to eliminate harmful stimuli and keep tissue healthy. However, healthy tissue is not always the end point of an immune response. Much evidence has been accumulated over the years, showing that the immune system has complex, diversified, and integrated functions that converge to maintaining tissue homeostasis, even in the absence of aggression, interacting with the tissue cells and allowing the functional maintenance of that tissue. One of the main cells known for their function in helping the immune response through the production of cytokines is CD4+ T lymphocytes. The cytokines produced by the different subtypes act not only on immune cells but also on tissue cells. Considering that tissues have specific mediators in their architecture, it is plausible that the presence and frequency of CD4+ T lymphocytes of specific subtypes (Th1, Th2, Th17, and others) maintain tissue homeostasis. In situations where homeostasis is disrupted, such as infections, allergies, inflammatory processes, and cancer, local CD4+ T lymphocytes respond to this disruption and, as in the healthy tissue, towards the equilibrium of tissue dynamics. CD4+ T lymphocytes can be manipulated by tumor cells to promote tumor development and metastasis, making them a prognostic factor in various types of cancer. Therefore, understanding the function of tissue-specific CD4+ T lymphocytes is essential in developing new strategies for treating tissue-specific diseases, as occurs in cancer. In this context, this article reviews the evidence for this hypothesis regarding the phenotypes and functions of CD4+ T lymphocytes and compares their contribution to maintaining tissue homeostasis in different organs in a steady state and during tumor progression.

High-throughput DNA sequence analysis elucidates novel insight into the genetic basis of adaptation in local sheep.

Understanding how evolutionary factors related to climate adaptation and human selection have influenced the genetic architecture of domesticated animals is of great interest in biology. In the current study, by using 304 whole genomes from different geographical regions (including Europe, north Africa, Southwest Asia, east Asia, west Africa, south Asia, east Africa, Australia and Turkey), We evaluate global sheep population dynamics in terms of genetic variation and population structure. We further conducted comparative population analysis to study the genetic underpinnings of climate adaption to local environments and also morphological traits. In order to identify genomic signals under selection, we applied fixation index (FST) and also nucleotide diversity (θπ) statistical measurements. Our results revealed several candidate genes on different chromosomes under selection for local climate adaptation (e.g. HOXC12, HOXC13, IRF1, FGD2 and GNAQ), body size (PDGFA, HMGA2, PDE3A) and also morphological related traits (RXFP2). The discovered candidate genes may offer newel insights into genetic underpinning of regional adaptation and commercially significant features in local sheep.

Is competitive ability the key adaptation to benign environments? Revisiting experiments on closely related species of tidal plants.

A central goal in biology is to understand which traits underlie adaptation to different environments. Yet, few studies have examined the relative contribution of competitive ability towards adaptive divergence among species occupying distinct environments. Here, we test the relative importance of competitive ability as an adaptation to relatively benign versus challenging environments, using previously published studies of closely related species pairs of primarily tidal plants subjected to reciprocal removal with transplant experiments in nature. Subordinate species typically occupy more challenging environments and showed consistent evidence for adaptation to challenging conditions, with no significant competitive effect on non-local, dominant species. In contrast, dominant species typically occupy relatively benign environments and performed significantly better than non-local, subordinate species that faced competition from the dominant species. Surprisingly, when the two species were not allowed to compete, the subordinate species performed as well as the dominant species in the benign environments where the subordinate species do not occur. These results suggest that competitive ability is the most important adaptation distinguishing the species that occupy relatively benign environments. The limited scope and number of suitable experimental studies encourage future work to test if these results are generalizable across taxa and environments.

Locomotion and morphological adaptations in the glass lizard Ophiodes cf. fragilis (Raddi, 1820) (Squamata: Anguidae).

There are few studies related to the biological and ecological aspects of the glass snake, a limbless lizard and with a wide geographic distribution. The aim of this study was to analyze the locomotion mode of specimens of Ophiodes cf. fragilis in different substrates and to investigate the morphological adaptations associated with this type of behavior. We observed that the analyzed specimens presented slide-push locomotion modes and lateral undulation in different substrates, using their hind limbs to aid locomotion in three of the four substrates analyzed. The bones of the hind limbs (proximal - femur - and distal - tibia and fibula) were present and highly reduced and the femur is connected to a thin pelvic girdle. Our data support that hind limbs observed in species of this genus are reduced rather than vestigial. The costocutaneous musculature was macroscopically absent. This is the first study of locomotor behavior and morphology associated with locomotion in Ophiodes, providing important information for studies on morphological evolution in the genus.

Proteome partitioning constraints in long-term laboratory evolution.

Adaptive laboratory evolution experiments provide a controlled context in which the dynamics of selection and adaptation can be followed in real-time at the single-nucleotide level. And yet this precision introduces hundreds of degrees-of-freedom as genetic changes accrue in parallel lineages over generations. On short timescales, physiological constraints have been leveraged to provide a coarse-grained view of bacterial gene expression characterized by a small set of phenomenological parameters. Here, we ask whether this same framework, operating at a level between genotype and fitness, informs physiological changes that occur on evolutionary timescales. Using a strain adapted to growth in glucose minimal medium, we find that the proteome is substantially remodeled over 40 000 generations. The most striking change is an apparent increase in enzyme efficiency, particularly in the enzymes of lower-glycolysis. We propose that deletion of metabolic flux-sensing regulation early in the adaptation results in increased enzyme saturation and can account for the observed proteome remodeling.

De novo motor learning creates structure in neural activity that shapes adaptation.

Animals can quickly adapt learned movements to external perturbations, and their existing motor repertoire likely influences their ease of adaptation. Long-term learning causes lasting changes in neural connectivity, which shapes the activity patterns that can be produced during adaptation. Here, we examined how a neural population's existing activity patterns, acquired through de novo learning, affect subsequent adaptation by modeling motor cortical neural population dynamics with recurrent neural networks. We trained networks on different motor repertoires comprising varying numbers of movements, which they acquired following various learning experiences. Networks with multiple movements had more constrained and robust dynamics, which were associated with more defined neural 'structure'-organization in the available population activity patterns. This structure facilitated adaptation, but only when the changes imposed by the perturbation were congruent with the organization of the inputs and the structure in neural activity acquired during de novo learning. These results highlight trade-offs in skill acquisition and demonstrate how different learning experiences can shape the geometrical properties of neural population activity and subsequent adaptation.

Comparative transcriptomic and physiological analyses unravel wheat source root adaptation to phosphorous deficiency.

Phosphorus (P) is a crucial macronutrient for plant growth and development. Basic metabolic processes regulate growth; however, the molecular detail of these pathways under low phosphorous (LP) in wheat is still unclear. This study aims to elucidate the varied regulatory pathways responses to LP stress in wheat genotypes. Phenotypic, physiological, and transcriptome analyses were conducted on Fielder (P efficient) and Ardito (P inefficient) wheat genotypes after four days of normal phosphorous (NP) and LP stress. In response to LP, Fielder outperformed Ardito, displaying higher chlorophyll content-SPAD values (13%), plant height (45%), stem diameter (12%), shoot dry weight (42%), and root biomass (75%). Root structure analysis revealed that Fielder had greater total root length (50%), surface area (56%), volume (15%), and diameter (4%) than Ardito under LP. These findings highlight Fielder's superior performance and adaptation to LP stress. Transcriptome analysis of wheat genotype roots identified 3029 differentially expressed genes (DEGs) in Fielder and 1430 in Ardito, highlighting LP-induced changes. Key DEGs include acid phosphatases (PAPs), phosphate transporters (PHT1 and PHO1), SPX, and transcription factors (MYB, bHLH, and WRKY). KEGG enrichment analysis revealed key pathways like plant hormones signal transduction, biosynthesis of secondary metabolites, and carbohydrate biosynthesis metabolism. This study unveils crucial genes and the intricate regulatory process in wheat's response to LP stress, offering genetic insights for enhancing plant P utilization efficiency.

Epitranscriptome insights into Riccia fluitans L. (Marchantiophyta) aquatic transition using nanopore direct RNA sequencing.

BACKGROUND: Riccia fluitans, an amphibious liverwort, exhibits a fascinating adaptation mechanism to transition between terrestrial and aquatic environments. Utilizing nanopore direct RNA sequencing, we try to capture the complex epitranscriptomic changes undergone in response to land-water transition. RESULTS: A significant finding is the identification of 45 differentially expressed genes (DEGs), with a split of 33 downregulated in terrestrial forms and 12 upregulated in aquatic forms, indicating a robust transcriptional response to environmental changes. Analysis of N6-methyladenosine (m6A) modifications revealed 173 m6A sites in aquatic and only 27 sites in the terrestrial forms, indicating a significant increase in methylation in the former, which could facilitate rapid adaptation to changing environments. The aquatic form showed a global elongation bias in poly(A) tails, which is associated with increased mRNA stability and efficient translation, enhancing the plant's resilience to water stress. Significant differences in polyadenylation signals were observed between the two forms, with nine transcripts showing notable changes in tail length, suggesting an adaptive mechanism to modulate mRNA stability and translational efficiency in response to environmental conditions. This differential methylation and polyadenylation underline a sophisticated layer of post-transcriptional regulation, enabling Riccia fluitans to fine-tune gene expression in response to its living conditions. CONCLUSIONS: These insights into transcriptome dynamics offer a deeper understanding of plant adaptation strategies at the molecular level, contributing to the broader knowledge of plant biology and evolution. These findings underscore the sophisticated post-transcriptional regulatory strategies Riccia fluitans employs to navigate the challenges of aquatic versus terrestrial living, highlighting the plant's dynamic adaptation to environmental stresses and its utility as a model for studying adaptation mechanisms in amphibious plants.

Genomic analysis uncovers novel candidate genes related to adaptation to tropical climates and milk production traits in native goats.

BACKGROUND: Since domestication, both evolutionary forces and human selection have played crucial roles in producing adaptive and economic traits, resulting in animal breeds that have been selected for specific climates and different breeding goals. Pakistani goat breeds have acquired genomic adaptations to their native climate conditions, such as tropical and hot climates. In this study, using next-generation sequencing data, we aimed to assess the signatures of positive selection in three native Pakistani goats, known as milk production breeds, that have been well adapted to their local climate. RESULTS: To explore the genomic relationship between studied goat populations and their population structure, whole genome sequence data from native goat populations in Pakistan (n = 26) was merged with available worldwide goat genomic data (n = 184), resulting in a total dataset of 210 individuals. The results showed a high genetic correlation between Pakistani goats and samples from North-East Asia. Across all populations analyzed, a higher linkage disequilibrium (LD) level (- 0.59) was found in the Pakistani goat group at a genomic distance of 1 Kb. Our findings from admixture analysis (K = 5 and K = 6) showed no evidence of shared genomic ancestry between Pakistani goats and other goat populations from Asia. The results from genomic selection analysis revealed several candidate genes related to adaptation to tropical/hot climates (such as; KITLG, HSPB9, HSP70, HSPA12B, and HSPA12B) and milk production related-traits (such as IGFBP3, LPL, LEPR, TSHR, and ACACA) in Pakistani native goat breeds. CONCLUSIONS: The results from this study shed light on the structural variation in the DNA of the three native Pakistani goat breeds. Several candidate genes were discovered for adaptation to tropical/hot climates, immune responses, and milk production traits. The identified genes could be exploited in goat breeding programs to select efficient breeds for tropical/hot climate regions.

Targeting Mycobacterium tuberculosis pH-driven adaptation.

Mycobacterium tuberculosis (Mtb) senses and adapts to host environmental cues as part of its pathogenesis. One important cue sensed by Mtb is the acidic pH of its host niche - the macrophage. Acidic pH induces widespread transcriptional and metabolic remodelling in Mtb. These adaptations to acidic pH can lead Mtb to slow its growth and promote pathogenesis and antibiotic tolerance. Mutants defective in pH-dependent adaptations exhibit reduced virulence in macrophages and animal infection models, suggesting that chemically targeting these pH-dependent pathways may have therapeutic potential. In this review, we discuss mechanisms by which Mtb regulates its growth and metabolism at acidic pH. Additionally, we consider the therapeutic potential of disrupting pH-driven adaptations in Mtb and review the growing class of compounds that exhibit pH-dependent activity or target pathways important for adaptation to acidic pH.

Pollen thermotolerance of a widespread plant, Lotus corniculatus, in response to climate warming: possible local adaptation of populations from different elevations.

One of the most vulnerable phases in the plant life cycle is sexual reproduction, which depends on effective pollen transfer, but also on the thermotolerance of pollen grains. Pollen thermotolerance is temperature-dependent and may be reduced by increasing temperature associated with global warming. A growing body of research has focused on the effect of increased temperature on pollen thermotolerance in crops to understand the possible impact of temperature extremes on yield. Yet, little is known about the effects of temperature on pollen thermotolerance of wild plant species. To fill this gap, we selected Lotus corniculatus s.l. (Fabaceae), a species common to many European habitats and conducted laboratory experiments to test its pollen thermotolerance in response to artificial increase in temperature. To test for possible local adaptation of pollen thermal tolerance, we compared data from six lowland (389-451 m a.s.l.) and six highland (841-1,030 m a.s.l.) populations. We observed pollen germination in vitro at 15 °C, 25 °C, 30 °C, and 40 °C. While lowland plants maintained a stable germination percentage across a broad temperature range (15-30 °C) and exhibited reduced germination only at extremely high temperatures (40 °C), highland plants experienced reduced germination even at 30 °C-temperatures commonly exceeded in lowlands during warm summers. This suggests that lowland populations of L. corniculatus may be locally adapted to higher temperature for pollen germination. On the other hand, pollen tube length decreased with increasing temperature in a similar way in lowland and highland plants. The overall average pollen germination percentage significantly differed between lowland and highland populations, with highland populations displaying higher germination percentage. On the other hand, the average pollen tube length was slightly smaller in highland populations. In conclusion, we found that pollen thermotolerance of L. corniculatus is reduced at high temperature and that the germination of pollen from plant populations growing at higher elevations is more sensitive to increased temperature, which suggests possible local adaptation of pollen thermotolerance.

Nonlethal deleterious mutation-induced stress accelerates bacterial aging.

Random mutagenesis, including when it leads to loss of gene function, is a key mechanism enabling microorganisms' long-term adaptation to new environments. However, loss-of-function mutations are often deleterious, triggering, in turn, cellular stress and complex homeostatic stress responses, called "allostasis," to promote cell survival. Here, we characterize the differential impacts of 65 nonlethal, deleterious single-gene deletions on Escherichia coli growth in three different growth environments. Further assessments of select mutants, namely, those bearing single adenosine triphosphate (ATP) synthase subunit deletions, reveal that mutants display reorganized transcriptome profiles that reflect both the environment and the specific gene deletion. We also find that ATP synthase α-subunit deleted (ΔatpA) cells exhibit elevated metabolic rates while having slower growth compared to wild-type (wt) E. coli cells. At the single-cell level, compared to wt cells, individual ΔatpA cells display near normal proliferation profiles but enter a postreplicative state earlier and exhibit a distinct senescence phenotype. These results highlight the complex interplay between genomic diversity, adaptation, and stress response and uncover an "aging cost" to individual bacterial cells for maintaining population-level resilience to environmental and genetic stress; they also suggest potential bacteriostatic antibiotic targets and -as select human genetic diseases display highly similar phenotypes, - a bacterial origin of some human diseases.