Regional dynamic cerebral autoregulation across anterior and posterior circulatory territories:A detailed exploration and its clinical implications

Cerebral autoregulation(CA)is the mechanism that maintains stable cerebral blood flow(CBF)despite fluctuations in systemic blood pressure,crucial for brain homeostasis.Recent evidence highlights distinct regional variations in CA between the anterior(carotid)and posterior(vertebrobasilar)circulations.Noninvasive neuromonitoring techniques,such as transcranial Doppler,transfer function analysis,and near-infrared spectroscopy,facilitate the dynamic assessment of CBF and autoregulation.Studies indicate a robust autoregulatory capacity in the anterior circulation,characterized by rapid adjustments in vascular resistance.On the contrary,the posterior circulation,mainly supplied by the vertebral arteries,may have a lower autoregulatory capacity.in acute brain injuries such as intracerebral and subarachnoid hemorrhage,and traumatic brain injuries,dynamic CA can be significantly altered in the posterior circulation.Proposed physiological mechanisms of impaired CA in the posterior circulation include:(1)Decreased sympathetic innervation of the vasculature impairing compensatory vasoreactivity;(2)Endothelial dysfunction;(3)Increased cerebral metabolic rate of oxygen consumption within the visual cortex causing CBFmetabolism(i.e.,neurovascular)uncoupling;and(4)Impaired blood-brain barrier integrity leading to impaired astrocytic mediated release of vasoactive substances(e.g.nitric oxide,potassium,and calcium ions).Furthermore,more research is needed on the effects of collateral circulation,as well as the circle of Willis variants,such as the fetal-type posterior cerebral artery,on dynamic CA.Improving our understanding of these mechanisms is crucial to improving the diagnosis,prognosis,and management of various cerebrovascular disorders.

FAM64A promotes HNSCC tumorigenesis by mediating transcriptional autoregulation of FOXM1

Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.

The utility of therapeutic hypothermia on cerebral autoregulation

Cerebral autoregulation(CA)dysfunction is a strong predictor of clinical outcome in patients with acute brain injury(ABI).CA dysfunction is a potential pathologic defect that may lead to secondary injury and worse functional outcomes.Early therapeutic hypothermia(TH)in patients with ABI is controversial.Many factors,including patient selection,timing,treatment depth,duration,and rewarming strategy,impact its clinical efficacy.Therefore,optimizing the benefit of TH is an important issue.This paper reviews the state of current research on the impact of TH on CA function,which may provide the basis and direction for CA-oriented target temperature management.

A GmNINa-miR172c-NNC1 Regulatory Network Coordinates the Nodulation and Autoregulation of Nodulation Pathways in Soybean

Symbiotic root nodules are root lateral organs of plants in which nitrogen-fixing bacteria(rhizobia)convert atmospheric nitrogen to ammonia.The formation and number of nodules in legumes are precisely controlled by a rhizobia-induced signal cascade and host-controlled autoregulation of nodulation(AON).However,how these pathways are integrated and their underlying mechanisms are unclear.Here,we report that microRNA172c(miR172c)activates soybean(Glycine max)R hizobia-induced CLE1(GmRICI)and GmRIC2 by removing the transcriptional repression of these genes by Nodule Number Control 1(NNC1),leading to the activation of the AON pathway.NNC1 interacts with GmNINa,the soybean ortholog of Lotus NODULE INCEPTION(NIN),and hampers its transcriptional activation o i G m RICI and GmRIC2.Importantly,GmNINa acts as a transcriptional activator of miR172c.Intriguingly,NNC1 can transcriptionally repress miR172c expression,adding a negative feedback loop into the NNC1 regulatory network.Moreover,GmNINa interacts with NNC1 and can relieve the NNC1-mediated repression of miR172c transcription.Thus,the GmNINa-miR172c-NNC1 network is a master switch that coordinately regulates and optimizes NF and AON signaling,supporting the balance between nodulation and AON in soybean.

Molecular Analysis of Legume Nodule Development and Autoregulation

Legumes are highly important food, feed and biofuel crops. With few exceptions, they can enter into an intricate symbiotic relationship with specific soil bacteria called rhizobia. This interaction results in the formation of a new root organ called the nodule in which the rhizobia convert atmospheric nitrogen gas into forms of nitrogen that are useable by the plant. The plant tightly controls the number of nodules it forms, via a complex root-to-shoot-to-root signaling loop called autoregulation of nodulation （AON）. This regulatory process involves peptide hormones, receptor kinases and small metabolites. Using modern genetic and genomic techniques, many of the components required for nodule formation and AON have now been isolated. This review addresses these recent findings, presents detailed models of the nodulation and AON processes, and identifies gaps in our understanding of these process that have yet to be fully explained.

Regulation of Resource Partitioning Coordinates Nitrogen and Rhizobia Responses and Autoregulation of Modulation in Medicago tmncatula

Understanding how plants respond to nitrogen in their environment is crucial for determining how they use it and how the nitrogen use affects other processes related to plant growth and development. Under nitrogen limitation the activity and affinity of uptake systems is increased in roots, and lateral root formation is regulated in order to adapt to low nitrogen levels and scavenge from the soil. Plants in the legume family can form associations with rhizobial nitrogen-fixing bacteria, and this association is tightly regulated by nitrogen levels. The effect of nitrogen on nodulation has been extensively investigated, but the effects of nodulation on plant nitrogen responses remain largely unclear. In this study, we integrated molecular and phenotypic data in the legume Medicago truncatula and determined that genes controlling nitrogen influx are differently expressed depending on whether plants are mock or rhizobia inoculated. We found that a functional autoregulation of nodulation pathway is required for roots to perceive, take up, and mobilize nitrogen as well as for normal root development. Our results together revealed that autoregulation of nodulation, root development, and the location of nitrogen are processes balanced by the whole plant system as part of a resource-partitioning mechanism.

The impact of central and obstructive respiratory events on cerebral oxygenation in adults with sleep disordered breathing

Obstructive sleep apnea(OSA)and central sleep apnea(CSA)are two main types of sleep disordered breathing(SDB).While the changes in cerebral hemodynamics triggered by OSA events have been well studied using near-infrared spectroscopy(NIRS),they are essentially unknown in CSA in adults.Therefore,in this study,we compared the changes in cerebral oxygenation between OSA and CSA events in adult patients using NIRS.Cerebral tissue oxygen saturation(StO_(2))in 13 severe SDB patients who had both CSA and OSA events was measured using frequency-domain NIRS.The changes in cerebral StO_(2)desaturation and blood volume(BV)in the¯rst hour of natural sleep were compared between different types of respiratory events(i.e.,277 sleep hypopneas,161 OSAs and 113 CSAs)with linear mixed-effect models controlling for confounders.All respiratory events occurred during non-rapid eye movement(NREM)sleep.We found that apnea events induced greater cerebral desaturations and BV°uctuations compared to hypopneas,but there was no difference between OSA and CSA.These results suggest that cerebral autoregulation in our patients are still capable to counteract the pathomechanisms of apneas,in particularly the negative intrathoracic pressure(ITP)caused by OSA events.Otherwise larger BV°uctuations in OSA compared to CSA should be observed due to the negative ITP that reduces cardiac stroke volume and leads to lower systematic blood supply.Our study suggests that OSA and CSA may have similar impact on cerebral oxygenation during NREM sleep in adult patients with SDB.

Revisiting normal perfusion pressure breakthrough in light of hemorrhage-induced vasospasm

Cerebral arteriovenous malformations(AVMs) have abnormally enlarged arteries and veins prone to spontaneous hemorrhage.Immediately following surgical excision of a cerebral AVM,even normal brain tissue surrounding the lesion is subject to hemorrhage,a phenomenon termed normal perfusion pressure breakthrough(NPPB) syndrome.According to this theory,arteries supplying cerebral AVMs become dilated and lose their capacity to dilate or constrict to autoregulate pressure.Acutely after removal of a cerebral AVM,excessive blood pressure in these arterial feeders can cause normal brain tissue to bleed.However,this theory remains controversial.We present a patient with a cerebral AVM that demonstrated cerebrovascular reactivity and argues against an assumption underlying the theory of NPPB syndrome.

Central blood pressure and chronic kidney disease

In this review, we focused on the relationship between central blood pressure and chronic kidney diseases(CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular(CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders(MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD.

COHERENT HEMODYNAMICS SPECTROSCOPY BASED ON A PACED BREATHING PARADIGM-REVISITED

A novel hemodynamic model has been recently introduced,which provides analytical relation-ships between the changes in cerebral blood volume(CBV),cerebral blood flow(CBF),andcerebral metabolic rate of oxy gen(CMRO2),and associat ed changes in the tissue concentrationsof oxy-and deoxy-hemoglobin(AO and AD)measured with near-infrared,spectroscopy(NIRS)[S.Fantini,Neuroimage 85,202-221(2014)].This novel model can be applied tomeasurements of the amplit ude and phase of induced hemodynamic oscillations as a function ofthe frequency of oscillation,realizing the novel technique of coherent hemodynamics spectroscopy(CHS)[S.Fantini,Neuroimage 85,202-221(2014);M.L.Pierro et al.,Neuroimage 85,222-233(2014)]:In a previous work,,we have demonstrated an in vivo application of CiHS on hunanSubjects during paced breat hing[M.L.Pierro et al,Neuroimage 85,222-233(2014)].In thiswork,we present a new analysis of the collected data duringpaced breat hing based on a slightlyrevised formulation of the hemodynamic model and ann efficient fitting procedure.While we haveinitially treated all 12 model parameindeependent,we have found that,in this new in-plementation of CHS,the number of independent is eight.In this article,we identifythe eight independent model parameters and,we show that our previous results are consistentwith the new formulation,once the individual parameters of the earlier analysis are combinedinto the new set of independent parameters.

Monitoring of rhythms in laset speckle data

While the laser speckle imaging(LSI)is a powerful tool for multiple biomedical applications,suchas monitoring of the blood flow,in many cases it can provide additional information when combined with spatio-temporal rhythm analysis.We demonstrate the application of GraphicsProcessing Units(GPU)-based rhythm analysis for the post procesing of LSI data,discuss therelevant structure of GPU-based computations,test the proposed technique on surrogate 3D data,and apply this approach to kidney blood fiow autoregulation.Experiments with surrogate data demonstrate the ability of the method to extract information about oscillation patterns fromnoisy data,as well as to detect the moving source of the rhythm.The analysis of kidney dataallow us to detect and to localize the dymamics arising from autoregulation processes at the levelof individual nephrons(tubuloglomerular feedback(TGF)rhythm),as well as to distinguishbetween the TGF-active and the TGF-silent zones.

Basic Principles Underlying Human Physiology

This is to declare that the article entitled “Basic Principles Underlying Human Physiology” [Health 6 (2014) 1816-1821] published in Health has been withdrawn due to the fact that the contents of this paper need further research and study. The article content (HTML and PDF) is removed and replaced with this announcement. The approval has been obtained from the author of this paper regarding the withdrawal of the article. In making this decision, the editorial office of Health is guided by the policies of the journal's editorial board and constrained by such legal requirements regarding libel, copyright infringement and plagiarism. In this context, Health strives to promote the circulation of scientific research, offering an ideal research publication platform to the world with specific regard to the ethical, moral and legal concerns involved. We would like to extend our sincere apologies for any inconvenience it may cause.

SYNTHESIS OF(4S,5R)-5-HYDROXY-4-DECANOLIDE.THE PROPOSED AUTOREGULATOR FROM STREPTOMYCES

(4S,5R)-5-Hydroxy-4-decanolide ,the proposed autoregulator from streptomyces Griseus was synthesized from an allyl alcohol 2,employ- ing the Sharpless kinetic resolution and the reaction of diethyl malonate with the epoxy compound as two key steps.

Negative Feedback Regulation of Auxin Signaling by ATHB8/ACL5-BUD2 Transcription Module

The role of auxin as main regulator of vascular differentiation is well established, and a direct correlation between the rate of xylem differentiation and the amount of auxin reaching the （pro）cambial cells has been proposed. It has been suggested that thermospermine produced by ACAULIS5 （ACL5） and BUSHY AND DWARF2 （BUD2） is one of the factors downstream to auxin contributing to the regulation of this process in Arabidopsis. Here, we provide an in-depth characterization of the mechanism through which ACL5 modulates xylem differentiation. We show that an increased level of ACL5 slows down xylem differentiation by negatively affecting the expression of homeodomain-leucine zipper （HD- ZIP） III and key auxin signaling genes. This mechanism involves the positive regulation of thermospermine biosynthesis by the HD-ZIP III protein ARABIDOPSIS THALIANA HOMEOBOX8 tightly controlling the expression of ACL5 and BUD2. In addition, we show that the HD-ZIP III protein REVOLUTA contributes to the increased leaf vascularization and long hypocotyl phenotype of acl5 likely by a direct regulation of auxin signaling genes such as LIKE AUXIN RESISTANT2 （LAX2） and LAX3. We propose that proper formation and differentiation of xylem depend on a balance between positive and negative feedback loops operating through HD-ZIP III genes.

Analysis of the downstream region of nodD3 P1 promoter by deletion and complementation tests in Sinorhizobium meliloti

In Sinorhizobium meliloti, the nodD3 gene is transcriptionally controlled by two promot-ers, P1 and P2. Under P1, there is a 660 bp sequence including a small open reading frame, ORF2, followed by the nodD3 coding region. Genetic analysis using the different deletions on the 3′ends of P1 downstream sequence showed that the downstream sequence +1—+125nt is es-sential for P1 expression. Complementation, mutations and nodulation tests demonstrated that the ORF2 auto-represses P1 expression, while the P1 downstream sequence +1—+125nt counteracts it.

The effect of sildenafil on retinal blood velocity in healthy subjects

Purpose:It has been suggested that Sildenafil may have beneficial therapeutic effects in the treatment of neurodegenerative disorders.The retinal circulation is of significant interest as a marker of cerebral vascular disease since the retinal and cerebral vasculatures share many morphological and physiological properties,yet only the retinal circulation can be directly visualized.Therefore,our aim was to assess the change induced by Sildenafil on retinal blood velocity.Methods:Retinal flow velocity was measured 0.5,3 and 6 h following administration of 100 mg of Sildenafil using the Retinal Function Imager.Results:No clinical change in either systemic blood pressure or retinal flow velocities were observed.However,when controlling for heart rate and blood pressure,a significant drop in venous flow velocity 6 h following treatment(mean drop 0.3±0.07;95%CI:0.44–0.56,P=0.023)was revealed.Conclusions:In healthy volunteers,retinal venous flow velocity was significantly reduced at the 6-h time point following Sildenafil treatment.No effect was observed on arterial retinal flow velocity.

The enantioselective synthesis of(4S,5S)-and(4S,5R)-5-hydroxy-4-decanolide,the autoregulators from Strepotomyces griseus

(4S,5S)-and(4S,5R)-5-Hydroxy-4-decanolide(1a and 1b),the proposed autoregula- tors from Strepotomyces Griseus were synthesized from a propargyl alcohol 2 in an overall yield of 30%,employing the Sharpless asymmetric epoxidation as the key step.