An increasing demand for energy and depleting petroleum sources has elevated the need for producing alternative renewable resources. Owing to the prominence of lignocellulosic biomass as ...bio-renewable and the most abundant resource on Earth, this critical review provides perceptions into the potential of lignocellulosic biomass for production of second generation (2G) ethanol and value added products in a biorefinery manner. The efficient utilization of all three components of lignocellulosic biomass (i.e., cellulose, hemicellulose and lignin) would play a significant role in the economic viability of cellulosic ethanol. The pretreatment method is the key to the success of bioconversion processes and greatly influences the economics of biorefinery process. Biotechnology tools and process engineering play pivotal roles in development of integrated processes for production of biofuels, biochemicals and biomaterials from lignocellulosic biomass. Although, lignocellulosic biorefinery has ample scopes, commercial production of biofuels and chemicals is still challenging. In this context, this review entails concept of lignocellulose biorefinery, latest developments in 2G ethanol production process, importance and market potential of 2G ethanol as renewable fuel and value added chemicals, integration of processes, challenges for integrated production of fuel together with value added chemicals and future directions.
Abstract Noradrenergic neurons of the brainstem extend projections throughout the neuraxis to modulate a wide range of processes including attention, arousal, autonomic control and sensory ...processing. A spinal projection from the locus coeruleus (LC) is thought to regulate nociceptive processing. To characterize and selectively manipulate the pontospinal noradrenergic neurons in rats, we implemented a retrograde targeting strategy using a canine adenoviral vector to express channelrhodopsin2 (CAV2-PRS-ChR2-mCherry). LC microinjection of CAV2-PRS-ChR2-mCherry produced selective, stable, transduction of noradrenergic neurons allowing reliable opto-activation in vitro . The ChR2-transduced LC neurons were opto-identifiable in vivo and functional control was demonstrated for >6 months by evoked sleep-wake transitions. Spinal injection of CAV2-PRS-ChR2-mCherry retrogradely transduced pontine noradrenergic neurons, predominantly in the LC but also in A5 and A7. A pontospinal LC (ps:LC) module was identifiable, with somata located more ventrally within the nucleus and with a discrete subset of projection targets. These ps:LC neurons had distinct electrophysiological properties with shorter action potentials and smaller afterhyperpolarizations compared to neurons located in the core of the LC. In vivo recordings of ps:LC neurons showed a lower spontaneous firing frequency than those in the core and they were all excited by noxious stimuli. Using this CAV2-based approach we have demonstrated the ability to retrogradely target, characterise and optogenetically manipulate a central noradrenergic circuit and show that the ps:LC module forms a discrete unit. This article is part of a Special Issue entitled SI: Noradrenergic System.
•REM sleep was discovered in the 1950s.•Many hypothalamic and brainstem areas have been found to contribute to REM sleep.•An up-to-date picture of REM-sleep-regulating circuits is reviewed.•A brief ...overview of computational models for REM sleep regulation is provided.•Outstanding issues for future studies are discussed.
Rapid eye movement (REM) sleep or paradoxical sleep is an elusive behavioral state. Since its discovery in the 1950s, our knowledge of the neuroanatomy, neurotransmitters and neuropeptides underlying REM sleep regulation has continually evolved in parallel with the development of novel technologies. Although the pons was initially discovered to be responsible for REM sleep, it has since been revealed that many components in the hypothalamus, midbrain, pons, and medulla also contribute to REM sleep. In this review, we first provide an up-to-date overview of REM sleep-regulating circuits in the brainstem and hypothalamus by summarizing experimental evidence from neuroanatomical, neurophysiological and gain- and loss-of-function studies. Second, because quantitative approaches are essential for understanding the complexity of REM sleep-regulating circuits and because mathematical models have provided valuable insights into the dynamics underlying REM sleep genesis and maintenance, we summarize computational studies of the sleep-wake cycle, with an emphasis on REM sleep regulation. Finally, we discuss outstanding issues for future studies.
The brainstem plays a crucial role in sleep-wake regulation. However, the ensemble dynamics underlying sleep regulation remain poorly understood. Here, we show slow, state-predictive brainstem ...ensemble dynamics and state-dependent interactions between the brainstem and the hippocampus in mice. On a timescale of seconds to minutes, brainstem populations can predict pupil dilation and vigilance states and exhibit longer prediction power than hippocampal CA1 neurons. On a timescale of sub-seconds, pontine waves (P-waves) are accompanied by synchronous firing of brainstem neurons during both rapid eye movement (REM) and non-REM (NREM) sleep. Crucially, P-waves functionally interact with CA1 activity in a state-dependent manner: during NREM sleep, hippocampal sharp wave-ripples (SWRs) precede P-waves. On the other hand, P-waves during REM sleep are phase-locked with ongoing theta oscillations and are followed by burst firing of CA1 neurons. This state-dependent global coordination between the brainstem and hippocampus implicates distinct functional roles of sleep.
electrophysiology is the gold standard technique used to investigate sub-second neural dynamics in freely behaving animals. However, monitoring cell-type-specific population activity is not a trivial ...task. Over the last decade, fiber photometry based on genetically encoded calcium indicators (GECIs) has been widely adopted as a versatile tool to monitor cell-type-specific population activity
. However, this approach suffers from low temporal resolution. Here, we combine these two approaches to monitor both sub-second field potentials and cell-type-specific population activity in freely behaving mice. By developing an economical custom-made system and constructing a hybrid implant of an electrode and a fiber optic cannula, we simultaneously monitor artifact-free mesopontine field potentials and calcium transients in cholinergic neurons across the sleep-wake cycle. We find that mesopontine cholinergic activity co-occurs with sub-second pontine waves, called P-waves, during rapid eye movement sleep. Given the simplicity of our approach, simultaneous electrophysiological recording and cell-type-specific imaging provides a novel and valuable tool for interrogating state-dependent neural circuit dynamics
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For the qualitative portion, I have conducted focus group discussions and in-depth interviews with a variety of acute coronary syndromes providers, including cardiologists, emergency department ...physicians, coronary care unit nurses, emergency department nurses, ambulance paramedics, and Kerala's director of the Department of Health Services. ...I am conducting a systematic policy review of pre-hospital acute coronary syndrome policies in India by obtaining information from governmental portals, like the National Rural Health Mission of the Ministry of Health and Family Welfare, and cardiology professional organizations, like the Cardiological Society of India and the Indian College of Cardiology.\n Nearly without exception, those of us engaged in this field recognize that "we cannot go it alone."
The aim of this study was to evaluate the predictors of left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement (TMVR).
LVOT obstruction is a major concern with ...TMVR, but limited data exist regarding its predictors and impact on outcomes.
Patients with pre-procedural multidetector row computed tomography (MDCT) undergoing TMVR for failed mitral bioprosthetic valves (valve-in-valve), annuloplasty rings (valve-in-ring), and mitral annular calcification (valve-in-MAC) were included in this study. Echocardiographic and procedural characteristics were recorded, and comprehensive assessment with MDCT was performed to identify the predictors of LVOT obstruction (defined as an increment of mean LVOT gradient ≥10 mm Hg from baseline). The new LVOT (neo-LVOT) area left after TMVR was estimated by embedding a virtual valve into the mitral annulus on MDCT, simulating the procedure.
Among 194 patients with pre-procedural MDCT undergoing TMVR (valve-in-valve, 107 patients; valve-in-ring, 50 patients; valve-in-MAC, 37 patients), LVOT obstruction was observed in 26 patients (13.4%), with a higher rate after valve-in-MAC than valve-in-ring and valve-in-valve (54.1% vs. 8.0% vs. 1.9%; p < 0.001). Patients with LVOT obstruction had significantly higher procedural mortality compared with those without LVOT obstruction (34.6% vs. 2.4%; p < 0.001). Receiver-operating characteristic curve analysis showed that an estimated neo-LVOT area ≤1.7 cm2 predicted LVOT obstruction with sensitivity of 96.2% and specificity of 92.3%.
LVOT obstruction after TMVR was associated with higher procedural mortality. A small estimated neo-LVOT area was significantly associated with LVOT obstruction after TMVR and may help identify patients at high risk for LVOT obstruction.
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Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from ...cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, these data suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.
•Markers of neutrophil activation (RETN, LCN2, HGF, IL-8, G-CSF) are among the most potent discriminators of critical illness in COVID-19.•Evidence of neutrophil activation precedes the onset of critical illness and predicts mortality in COVID-19.
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Neurofibromatosis type 1 (NF1) is an autosomal genetic disorder. Patients with NF1 are associated with mono-allelic loss of the tumor suppressor gene NF1 in their germline, which predisposes them to ...develop a wide array of benign lesions. Intriguingly, recent sequencing efforts revealed that the NF1 gene is frequently mutated in multiple malignant tumors not typically associated with NF1 patients, suggesting that NF1 heterozygosity is refractory to at least some cancer types. In two orthogonal mouse models representing NF1- and non-NF1-related tumors, we discover that an Nf1
microenvironment accelerates the formation of benign tumors but impairs further progression to malignancy. Analysis of benign and malignant tumors commonly associated with NF1 patients, as well as those with high NF1 gene mutation frequency, reveals an antagonistic role for NF1 heterozygosity in tumor initiation and malignant transformation and helps to reconciliate the role of the NF1 gene in both NF1 and non-NF1 patient contexts.
Cardiac allograft vasculopathy: A review Lee, Michael S.; Tadwalkar, Rigved V.; Fearon, William F. ...
Catheterization and cardiovascular interventions,
December 1, 2018, 2018-12-01, 2018-12-00, 20181201, Volume:
92, Issue:
7
Journal Article
Peer reviewed
Cardiac allograft vasculopathy (CAV) is a complex disease that remains a significant cause of morbidity and mortality after orthotopic heart transplantation (OHT). Originating as a result of ...inflammatory response, the development and progression of CAV is attributed to endothelial dysfunction, cellular infiltration, and a wide‐range of genetic and patient factors. The detection of CAV remains a diagnostic challenge, as symptoms can be variable or absent. While coronary angiography remains the initial test of choice for the diagnosis and surveillance of CAV, intravascular imaging (either by ultrasound or optical coherence tomography) and physiologic assessments are useful adjuncts in the cardiac catheterization laboratory. Positron emission tomography, computed tomographic, and magnetic resonance imaging may have a role increasing the time interval between invasive screening tests for prognosis. Medical management should include a statin, vasodilator, and tailored immunosuppressive regimen that maximally decrease allograft rejection and CAV progression while causing minimal side effects. Patients that are less responsive to pharmacotherapy should be considered for invasive management with percutaneous coronary intervention. Although surgical revascularization is a poor option, repeat OHT is the only definitive treatment option but given its morbidity should be reserved for a highly selected patient population.
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