Diverse fates of ancient horizontal gene transfers in extremophilic red algae.

Horizontal genetic transfer (HGT) is a common phenomenon in eukaryotic genomes. However, the mechanisms by which HGT-derived genes persist and integrate into other pathways remain unclear. This topic is of significant interest because, over time, the stressors that initially favoured the fixation of HGT may diminish or disappear. Despite this, the foreign genes may continue to exist if they become part of a broader stress response or other pathways. The conventional model suggests that the acquisition of HGT equates to adaptation. However, this model may evolve into more complex interactions between gene products, a concept we refer to as the 'Integrated HGT Model' (IHM). To explore this concept further, we studied specialized HGT-derived genes that encode heavy metal detoxification functions. The recruitment of these genes into other pathways could provide clear examples of IHM. In our study, we exposed two anciently diverged species of polyextremophilic red algae from the Galdieria genus to arsenic and mercury stress in laboratory cultures. We then analysed the transcriptome data using differential and coexpression analysis. Our findings revealed that mercury detoxification follows a 'one gene-one function' model, resulting in an indivisible response. In contrast, the arsH gene in the arsenite response pathway demonstrated a complex pattern of duplication, divergence and potential neofunctionalization, consistent with the IHM. Our research sheds light on the fate and integration of ancient HGTs, providing a novel perspective on the ecology of extremophiles.

Heterogeneity in Measures of Illness among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Explained by Clinical Practice: A Study in Seven U.S. Specialty Clinics.

Background: One of the goals of the Multi-site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM) study was to evaluate whether clinicians experienced in diagnosing and caring for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recognized the same clinical entity. Methods: We enrolled participants from seven specialty clinics in the United States. We used baseline data (n = 465) on standardized questions measuring general clinical characteristics, functional impairment, post-exertional malaise, fatigue, sleep, neurocognitive/autonomic symptoms, pain, and other symptoms to evaluate whether patient characteristics differed by clinic. Results: We found few statistically significant and no clinically significant differences between clinics in their patients' standardized measures of ME/CFS symptoms and function. Strikingly, patients in each clinic sample and overall showed a wide distribution in all scores and measures. Conclusions: Illness heterogeneity may be an inherent feature of ME/CFS. Presenting research data in scatter plots or histograms will help clarify the challenge. Relying on case-control study designs without subgrouping or stratification of ME/CFS illness characteristics may limit the reproducibility of research findings and could obscure underlying mechanisms.

Molecular Mechanisms Associated with the Development of the Metritis Complex in Dairy Cattle.

The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association study was performed using a single-locus mixed linear model of 1967 genotypes (624,460 SNPs) and metritis complex records. Then, in-silico functional analyses were performed to detect biological mechanisms and pathways associated with the development of MC. The ATP8A2, COX16, AMN, and TRAF3 genes, located on chromosomes 12, 10, and 21, were associated with MC at p ≤ 0.0001. These genes are involved in the regulation of cholesterol metabolism in the stromal tissue of the uterus, which can be directly associated with the mode of transmission for pathogens causing the metritis complex. The modulation of cholesterol abundance alters the efficiency of virulence factors and may affect the susceptibility of the host to infection. The SIPA1L1, DEPDC5, and RNF122 genes were also significantly associated with MC at p ≤ 0.0001 and are involved in the PI3k-Akt pathway, responsible for activating the autophagic processes. Thus, the dysregulation of these genes allows for unhindered bacterial invasion, replication, and survival within the endometrium.

Complete genome sequences of two avian pathogenic Escherichia coli strains isolated from broilers exhibiting colibacillosis in Mississippi.

We report the whole-genome sequences of Escherichia coli strains APEC-O2-MS1266 and APEC-O2-MS1657 isolated from the liver and heart of infected broilers in Mississippi State, US. The genomic information of these two causative strains may provide a valuable reference for comparative studies of avian pathogenic E. coli.

Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA. METHODS: The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study's initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment. RESULTS: Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists. CONCLUSIONS: The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated. TRIAL REGISTRATION: NCT04539964; August 31, 2020.

Achieving Surgical, Obstetric, Trauma, and Anesthesia (SOTA) care for all in South Asia.

South Asia is a demographically crucial, economically aspiring, and socio-culturally diverse region in the world. The region contributes to a large burden of surgically-treatable disease conditions. A large number of people in South Asia cannot access safe and affordable surgical, obstetric, trauma, and anesthesia (SOTA) care when in need. Yet, attention to the region in Global Surgery and Global Health is limited. Here, we assess the status of SOTA care in South Asia. We summarize the evidence on SOTA care indicators and planning. Region-wide, as well as country-specific challenges are highlighted. We also discuss potential directions-initiatives and innovations-toward addressing these challenges. Local partnerships, sustained research and advocacy efforts, and politics can be aligned with evidence-based policymaking and health planning to achieve equitable SOTA care access in the South Asian region under the South Asian Association for Regional Cooperation (SAARC).

Generalization of In-Place Balance Perturbation Training in People With Parkinson Disease.

BACKGROUND AND PURPOSE: Reactive balance training improves reactive postural control in people with Parkinson disease (PwPD). However, the extent to which reactive balance training generalizes to a novel, unpracticed reactive balance task is unknown. This study aimed to determine whether reactive training stepping through support surface translations can be generalized to an unpracticed, instrumented tether-release task. METHODS: Twenty-five PwPD (70.52 years ± 7.15; Hoehn and Yahr range 1-3) completed a multiple baseline, open-label, uncontrolled pre-post intervention study. Stepping was trained through a 2-week (6-session) intervention with repeated support surface translations. Performance on an untrained tether-release task (generalization task) was measured at 2 baseline assessments (B1 and B2, 2 weeks apart), immediately after the intervention (P1), and 2 months after training (P2). The tether-release task outcomes were the anterior-posterior margin of stability (MOS), step length, and step latency during backward and forward steps. RESULTS: After support surface translation practice, tether-release stepping performance improved in MOS, step length, and step latency for both backward and forward steps compared to baseline (P < 0.05). Improvements in MOS and step length during backward and forward steps in the tether-release task, respectively, were related to stepping changes in the practiced task. However, the improvements in the generalization task were not retained for 2 months. DISCUSSION AND CONCLUSIONS: These findings support short-term generalization from trained balance tasks to novel, untrained tasks. These findings contribute to our understanding of the effects and generalization of reactive step training in PwPD.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content available at http://links.lww.com/JNPT/A465).

Associating white matter microstructural integrity and improvements in reactive stepping in people with Parkinson's Disease.

Reactive steps are rapid responses after balance challenges. People with Parkinson's Disease (PwPD) demonstrate impaired reactive stepping, increasing fall-risk. Although PwPD can improve steps through practice, the neural mechanisms contributing to improved reactive stepping are poorly understood. This study investigated white-matter correlates of responsiveness to reactive step training in PwPD. In an eighteen-week multiple-baseline study, participants (n = 22) underwent baseline assessments (B1 and B2 two-weeks apart), a two-week training protocol, and post-training assessments immediately (P1) and two-months (P2) post-training. Assessments involved three backward reactive step trials, measuring anterior-posterior margin of stability (AP MOS), step length, and step latency. Tract-Based Spatial Statistics correlated white-matter integrity (fractional anisotropy (FA) and radial diffusivity (RD)) with retained (P2-B2) and immediate improvements (P1-B2) in stepping. Significant and sustained improvements in step length and AP MOS were observed. Greater retention of step length improvement correlated with increased FA in the left anterior thalamic radiation (ATR), left posterior thalamic radiation (PTR), left superior longitudinal fasciculus (SLF), and right inferior longitudinal fasciculus (ILF). Step latency retention was associated with lower RD in the left posterior corona radiata and left PTR. Immediate improvements in AP MOS correlated with increased FA of the right ILF, right SLF, and right corticospinal tract. Immediate step length improvements were associated with increased FA in right and left ATR and right SLF. These findings highlight the importance of white-matter microstructural integrity in motor learning and retention processes in PD and could aid in identifying individuals with PD who would benefit most from balance rehabilitation.

Global Neurosurgery at the 76th World Health Assembly (2023): First Neurosurgery-Driven Resolution Calls for Micronutrient Fortification to Prevent Spina Bifida.

Since 2018, a neurosurgery delegation has been actively engaged and consistently present at the World Health Assembly. Recognizing the growing impact of neurosurgical diseases, the neurosurgery delegation participated in the 76th World Health Assembly in May 2023, advocating for timely, safe, and affordable global neurosurgical care. The delegation focused on forging new collaborations, strengthening the World Health Organization-World Federation of Neurosurgical Societies official relations, and actively supporting resolutions that impact the neurosurgical patients. However, there is a long advocacy journey ahead to address unmet neurosurgical needs. Patient-centered advocacy is an inherent task of our profession and the essence of the Global Neurosurgery Bogota Declaration of 2016. The highlight of the 76th World Health Assembly was the adoption of the first neurosurgery-driven resolution calling for micronutrient fortification to prevent spina bifida and other micronutrient deficiencies. For the last 4 years, the Global Alliance for Prevention of Spina Bifida, a group spearheaded by neurosurgeons, advocated for spina bifida prevention. This Alliance collaborated with many stakeholders, notably, the Colombian government to promote the resolution: "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification." This is a proud milestone for the neurosurgical profession. There are many strategies available for neurosurgeons, when working together with elected leaders, other stakeholders, and allied professionals, to implement initiatives that can prevent future cases of spina bifida and other neurological disorders and reduce the burden of neurosurgical disease.

Stability Changes in Fall-Prone Individuals With Parkinson Disease Following Reactive Step Training.

BACKGROUND AND PURPOSE: Poor reactive steps may lead to falls in people with Parkinson disease (PwPD). However, whether reactive steps can be improved in PwPD at risk for falls or whether step training reduces falls remains unclear. This study aimed to determine whether 2 weeks of reactive step training result in (1) immediate and retained improvements in stepping and (2) fewer prospective falls in PwPD at fall risk. METHODS: Twenty-five PwPD (70.52 years ± 7.15; Hoehn & Yahr range 1-3) at risk for falls completed a multiple baseline, open-label, uncontrolled pre-/postintervention study. Stepping performance was assessed at 2 baseline assessments (B1 and B2) followed by a 2-week, 6-session training protocol. Stepping was assessed immediately (P1) and 2 months after training (P2). Primary outcomes were anterior-posterior margin of stability (MOS), step length, and step latency during backward stepping. Fall frequency was measured for 2 months before and after training. RESULTS: MOS during backward steps was significantly larger (better) after training ( P < 0.001, d = 0.83), and improvements were retained for 2 months ( P = 0.04, d = 0.66). Step length was not statistically significant different after training ( P = 0.13, d = 0.46) or at follow-up ( P = 0.08, d = 0.62), although effect sizes were medium and large, respectively. Step latency improved after initial exposure ( P = 0.01, d = 0.60) but not following training ( P = 0.43, d = 0.35). Twelve participants experienced fewer falls after training than before (10 = no change, 5 = increase; P = 0.12). Greater improvements in MOS were related to fewer falls ( P = 0.04). DISCUSSION AND CONCLUSIONS: Two weeks of reactive step training resulted in immediate and retained improvements in some reactive stepping outcomes in PwPD at risk for falls and may reduce fall risk. Reactive step training may be a viable approach to reduce falls in PwPD.

Using objective measures to examine the effect of suspect-filler similarity on eyewitness identification performance.

When selecting fillers to include in a police lineup, one must consider the level of similarity between the suspect and potential fillers. In order to reduce misidentifications, an innocent suspect should not stand out. Therefore, it is important that the fillers share some degree of similarity. Importantly, increasing suspect-filler similarity too much will render the task too difficult reducing correct identifications of a guilty suspect. Determining how much similarity yields optimal identification performance is the focus of the proposed study. Extant research on lineup construction has provided somewhat mixed results. In part, this is likely due to the subjective nature of similarity, which forces researchers to define similarity in relative terms. In the current study, we manipulate suspect-filler similarity via a multidimensional scaling model constructed using objective facial measurements. In doing so, we test the "propitious heterogeneity" and the diagnostic-feature-detection hypotheses which predict an advantage of lineups with low-similarity fillers in terms of discriminability. We found that filler similarity did not affect discriminability. We discuss limitations and future directions.

Cognitive Predictors of Responsiveness to Reactive Step Training in People with Parkinson's Disease at Fall-Risk.

Reactive stepping can be improved in people with Parkinson's Disease (PwPD). However, there is variability in the responsiveness to such training. This study examined if cognition could predict the responsiveness of PwPD to a two-week reactive step training intervention. 25 PwPD (70.52 years ± 7.15; Hoehn & Yahr range 1-3) at risk for falls completed a multiple baseline, open-label, uncontrolled pre-post intervention study. Reactive stepping was trained through a two-week (six-session) intervention with repeated support surface translations. Stepping performance was measured at two baseline assessments (B1 and B2), immediately after the intervention (P1), and two months after training (P2). Primary stepping outcomes were anterior-posterior margin of stability (MOS), step length, and step latency during backward steps. The primary aim assessed whether global cognition (Scales for Outcomes in Parkinson's Disease-Cognition - SCOPA-COG, & Montreal Cognitive Assessment - MoCA) was related to two-month retention of improvements in reactive stepping after practice. The secondary aim explored whether specific cognitive domains predicted retained stepping improvements, including attention/working memory, executive function, language, memory, and visuospatial function. Greater baseline global cognition was related to better two-month retention of step length improvements (SCOPA-COG: p = 0.002, f2 = 0.31; MoCA: p = 0.002, f2 = 0.38). However, only SCOPA-COG retained statistical significance after p-value adjustment for multiple comparisons (p = 0.04). Optimal cut-point analysis revealed that a SCOPA-COG threshold of 31 or higher was optimal for identifying individuals likely to retain improvement. Specific cognitive domains did not predict changes in reactive stepping outcomes. Participants with greater baseline global cognition, particularly as measured by SCOPA-COG, demonstrated greater retention of improvements in reactive stepping. In this cohort, a SCOPA-COG threshold of 31 could predict individuals likely to benefit from the intervention. These findings highlight the potential of cognitive screening to identify people more or less likely to benefit from reactive balance training.

Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells.

Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.

Myalgic Encephalomyelitis-Chronic Fatigue Syndrome Common Data Element item content analysis.

INTRODUCTION: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystem chronic disease estimated to affect 836,000-2.5 million individuals in the United States. Persons with ME/CFS have a substantial reduction in their ability to engage in pre-illness levels of activity. Multiple symptoms include profound fatigue, post-exertional malaise, unrefreshing sleep, cognitive impairment, orthostatic intolerance, pain, and other symptoms persisting for more than 6 months. Diagnosis is challenging due to fluctuating and complex symptoms. ME/CFS Common Data Elements (CDEs) were identified in the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) Common Data Element Repository. This study reviewed ME/CFS CDEs item content. METHODS: Inclusion criteria for CDEs (measures recommended for ME/CFS) analysis: 1) assesses symptoms; 2) developed for adults; 3) appropriate for patient reported outcome measure (PROM); 4) does not use visual or pictographic responses. Team members independently reviewed CDEs item content using the World Health Organization International Classification of Functioning, Disability and Health (ICF) framework to link meaningful concepts. RESULTS: 119 ME/CFS CDEs (measures) were reviewed and 38 met inclusion criteria, yielding 944 items linked to 1503 ICF meaningful concepts. Most concepts linked to ICF Body Functions component (b-codes; n = 1107, 73.65%) as follows: Fatiguability (n = 220, 14.64%), Energy Level (n = 166, 11.04%), Sleep Functions (n = 137, 9.12%), Emotional Functions (n = 131, 8.72%) and Pain (n = 120, 7.98%). Activities and Participation concepts (d codes) accounted for a smaller percentage of codes (n = 385, 25.62%). Most d codes were linked to the Mobility category (n = 69, 4.59%) and few items linked to Environmental Factors (e codes; n = 11, 0.73%). DISCUSSION: Relatively few items assess the impact of ME/CFS symptoms on Activities and Participation. Findings support development of ME/CFS-specific PROMs, including items that assess activity limitations and participation restrictions. Development of psychometrically-sound, symptom-based item banks administered as computerized adaptive tests can provide robust assessments to assist primary care providers in the diagnosis and care of patients with ME/CFS.

A multicenter virome analysis of blood, feces, and saliva in myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect 0.4%-2.5% of the global population. Most cases are unexplained; however, some patients describe an antecedent viral infection or response to antiviral medications. We report here a multicenter study for the presence of viral nucleic acid in blood, feces, and saliva of patients with ME/CFS using polymerase chain reaction and high-throughput sequencing. We found no consistent group-specific differences other than a lower prevalence of anelloviruses in cases compared to healthy controls. Our findings suggest that future investigations into viral infections in ME/CFS should focus on adaptive immune responses rather than surveillance for viral gene products.

Freezing of Gait in Parkinson's Disease: Implications for Dual-Task Walking.

BACKGROUND: The simultaneous completion of multiple tasks (dual-tasking, DT) often leads to poorer task performance (DT cost, DTC). People with Parkinson's disease (PwPD) exhibit difficulty with DT, and DTC may be particularly pronounced in PwPD with freezing of gait (FOG). OBJECTIVE: This study assessed the relationship between FOG status and DTC during gait. METHODS: Gait parameters were collected using inertial sensors in 106 PwPD (off-medication), including definite-freezers (dFOG; n = 25), possible-freezers (pFOG; n = 16), and non-freezers (nFOG; n = 65) during single (ST)-and DT walking. RESULTS: PwPD with dFOG had larger (worse) DTC than nFOG for foot-strike angle, stride length, toe-off angle, variability of foot-strike angle, and arm range of motion (ROM). After accounting for covariates, DTC for toe-off angle and stride length remained worse in PwPD who freeze. Worse cognition predicted larger DTC for stride length, gait cycle duration, gait speed, and step duration across groups. Men had larger DTC compared to women for gait speed, variability in foot-strike angle, stride length, and arm ROM. Increased variability in gait speed DTC was associated with increased disease severity. CONCLUSION: These findings provide additional support that PwPD who freeze may rely on greater cortical control for the execution of specific gait metrics. The results also underscore the importance of considering cognition when assessing DT ability in PwPD.

Effects of voluntary, and forced exercises on neurotrophic factors and cognitive function in animal models of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the elderly. Cognitive dysfunction represents a common and challenging non-motor symptom for people with Parkinson's disease. The number of neurotrophic proteins in the brain is critical in neurodegenerative diseases such as Parkinson's. This research aims to compare the effects of two types of exercise, forced and voluntary, on spatial memory and learning and neurochemical factors (CDNF and BDNF). METHODS: In this research, 60 male rats were randomly divided into six groups (n = 10): the control (CTL) group without exercise, the Parkinson's groups without and with forced (FE) and voluntary (VE) exercises, and the sham groups (with voluntary and forced exercise). The animals in the forced exercise group were placed on the treadmill for four weeks (five days a week). At the same time, voluntary exercise training groups were placed in a special cage equipped with a rotating wheel. At the end of 4 weeks, learning and spatial memory were evaluated with the Morris water maze test. BDNF and CDNF protein levels in the hippocampus were measured by the ELISA method. RESULTS: The results showed that although the PD group without exercise was at a significantly lower level than other groups in terms of cognitive function and neurochemical factors, both types of exercise, could improve these problems. CONCLUSION: According to our results, 4 weeks of voluntary and forced exercises were all found to reverse the cognitive impairments of PD rats.

Domestication over Speciation in Allopolyploid Cotton Species: A Stronger Transcriptomic Pull.

Cotton has been domesticated independently four times for its fiber, but the genomic targets of selection during each domestication event are mostly unknown. Comparative analysis of the transcriptome during cotton fiber development in wild and cultivated materials holds promise for revealing how independent domestications led to the superficially similar modern cotton fiber phenotype in upland (G. hirsutum) and Pima (G. barbadense) cotton cultivars. Here we examined the fiber transcriptomes of both wild and domesticated G. hirsutum and G. barbadense to compare the effects of speciation versus domestication, performing differential gene expression analysis and coexpression network analysis at four developmental timepoints (5, 10, 15, or 20 days after flowering) spanning primary and secondary wall synthesis. These analyses revealed extensive differential expression between species, timepoints, domestication states, and particularly the intersection of domestication and species. Differential expression was higher when comparing domesticated accessions of the two species than between the wild, indicating that domestication had a greater impact on the transcriptome than speciation. Network analysis showed significant interspecific differences in coexpression network topology, module membership, and connectivity. Despite these differences, some modules or module functions were subject to parallel domestication in both species. Taken together, these results indicate that independent domestication led G. hirsutum and G. barbadense down unique pathways but that it also leveraged similar modules of coexpression to arrive at similar domesticated phenotypes.

Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a multisystem chronic illness characterized by severe muscle fatigue, pain, dizziness, and brain fog. Many patients with ME/CFS experience orthostatic intolerance (OI), which is characterized by frequent dizziness, light-headedness, and feeling faint while maintaining an upright posture. Despite intense investigation, the molecular mechanism of this debilitating condition is still unknown. OI is often manifested by cardiovascular alterations, such as reduced cerebral blood flow, reduced blood pressure, and diminished heart rate. The bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of endothelial nitric oxide synthase (eNOS) enzyme, is tightly coupled with cardiovascular health and circulation. To explore the role of BH4 in ME/CFS, serum samples of CFS patients (n = 32), CFS patients with OI only (n = 10; CFS + OI), and CFS patients with both OI and small fiber polyneuropathy (n = 12; CFS + OI + SFN) were subjected to BH4 ELISA. Interestingly, our results revealed that the BH4 expression is significantly high in CFS, CFS + OI, and CFS + OI + SFN patients compared to age-/gender-matched controls. Finally, a ROS production assay in cultured microglial cells followed by Pearson correlation statistics indicated that the elevated BH4 in serum samples of CFS + OI patients might be associated with the oxidative stress response. These findings suggest that the regulation of BH4 metabolism could be a promising target for understanding the molecular mechanism of CFS and CFS with OI.