Dehalobacter (Firmicutes) encompass obligate organohalide‐respiring bacteria used for bioremediation of groundwater contaminated with halogenated organics. Various aspects of their biochemistry ...remain unknown, including the identities and interactions of respiratory proteins. Here, we sequenced the genome of Dehalobacter sp. strain 8M and analysed its protein expression. Strain 8M encodes 22 reductive dehalogenase homologous (RdhA) proteins. RdhA D8M_v2_40029 (TmrA) was among the two most abundant proteins during growth with trichloromethane and 1,1,2‐trichloroethane. To examine interactions of respiratory proteins, we used blue native gel electrophoresis together with dehalogenation activity tests and mass spectrometry. The highest activities were found in gel slices with the highest abundance of TmrA. Protein distributions across gel lanes provided biochemical evidence that the large and small subunits of the membrane‐bound NiFe uptake hydrogenase (HupL and HupS) interacted strongly and that HupL/S interacted weakly with RdhA. Moreover, the interaction of RdhB and membrane‐bound b‐type cytochrome HupC was detected. RdhC proteins, often encoded in rdh operons but without described function, migrated in a protein complex not associated with HupL/S or RdhA. This study provides the first biochemical evidence of respiratory protein interactions in Dehalobacter, discusses implications for the respiratory architecture and advances the molecular comprehension of this unique respiratory chain.
Dehalobacter can respire with chlorinated methanes (chloroform) and ethanes. Genome sequencing, proteome analyses and enzymatic assays identify TmrA as the responsible enzyme. It is organized in a larger membrane‐bound respiratory complex. RdhC, a protein encoded in the same operon, appears to be another membrane‐bound electron‐transferring protein but its interaction with the respiratory complex is inconclusive.
LSTVs are common within the spine, and their association with low back pain has been debated in the literature for nearly a century. LSTVs include sacralization of the lowest lumbar vertebral body ...and lumbarization of the uppermost sacral segment. These vertebral bodies demonstrate varying morphology, ranging from broadened transverse processes to complete fusion. Low back pain associated with an LSTV may arise from the level above the transition, the contralateral facet when unilateral, and/or the anomalous articulation when present. Although this association is still somewhat controversial, beyond dispute is the importance of identifying an LSTV in patients in whom a surgical or interventional procedure is planned. This is essential to avoid an intervention or surgery at an incorrect level. In this article, each of these issues will be addressed with attention to identifying and correctly numbering LSTVs as well as detecting imaging findings related to the genesis of low back pain.
Background. Mortality associated with surgery for phaeochromocytoma has dramatically decreased over the last decades. Many factors contributed to the dramatic decline of the mortality rate, and the ...influence of an α-receptor blockade is unclear and has never been tested in a randomized trial. We evaluated intraoperative haemodynamic conditions and the incidence of complications in patients with and without α-receptor blockade undergoing surgery for catecholamine producing tumours.
Methods. Haemodynamic conditions and perioperative complications were assessed in 110 patients with (B) and 166 without (N) α-receptor blockade. Data were analysed as a consecutive case series of 303 cases and subsequently via propensity score matching, and presented as mean and confidence interval (CI).
Results. No difference in maximal intraoperative systolic arterial pressures (B = 178 mm Hg (CI 169-187) vs N = 185 mm Hg (CI 177-193; P = 0.2542) and hypertensive episodes above 250 mm Hg were found (P = 0.7474) for the closed case series. No major complications occurred. Propensity score matching (75 pairs) revealed a significant difference of 17 mm Hg in maximal intraoperative systolic bp for these selected pairs (P = 0.024).
Conclusions. Only a slight difference in mean maximal systolic arterial pressure was detected between patients with or without an α-receptor blockade. There was no difference in the incidence of excessive hypertensive episodes between groups and no major complications occurred. The basis for the general recommendation of perioperative α- receptor blockade for phaeochromocytoma surgery demands further study.
Pupillary measures have been linked to arousal and attention as well as activity in the brainstem's locus coeruleus norepinephrine (LC-NE) system. Similarly, there is evidence that evoked EEG ...responses, such as the P3, might have LC-NE activity as their basis. Since it is not feasible to record electrophysiological data directly from the LC in humans due to its location in the brainstem, an open question has been whether pupillary measures and EEG variability can be linked in a meaningful way to shed light on the nature of the LC-NE role in attention and arousal. We used an auditory oddball task with a data-driven approach to learn task-relevant projections of the EEG, for windows of data spanning the entire trial. We investigated linear and quadratic relationships between the evoked EEG along these projections and both prestimulus (baseline) and poststimulus (evoked dilation) pupil diameter measurements. We found that baseline pupil diameter correlates with early (175-200 ms) and late (350-400 ms) EEG component variability, suggesting a linear relationship between baseline (tonic) LC-NE activity and evoked EEG. We found no relationships between evoked EEG and evoked pupil dilation, which is often associated with evoked (phasic) LC activity. After regressing out reaction time (RT), the correlation between EEG variability and baseline pupil diameter remained, suggesting that such correlation is not explainable by RT variability. We also investigated the relationship between these pupil measures and prestimulus EEG alpha activity, which has been reported as a marker of attentional state, and found a negative linear relationship with evoked pupil dilation. In summary, our results demonstrate significant relationships between prestimulus and poststimulus neural and pupillary measures, and they provide further evidence for tight coupling between attentional state and evoked neural activity and for the role of cortical and subcortical networks underlying the process of target detection.
Position isomerism is ubiquitous in atmospheric oxidation reactions. Therefore, we have compared surface-active oxygenated amphiphilic isomers (1- and 3-pentanol) at the aqueous surface with surface- ...and chemically sensitive X-ray photoelectron spectroscopy (XPS), which reveals information about the surface structure on a molecular level. The experimental data are complemented with molecular dynamics (MD) simulations. A concentration-dependent orientation and solvation of the amphiphiles at the aqueous surface is observed. At bulk concentrations as low as around 100 mM, a monolayer starts to form for both isomers, with the hydroxyl groups pointing towards the bulk water and the alkyl chains pointing towards the vacuum. The monolayer (ML) packing density of 3-pentanol is approx. 70% of the one observed for 1-pentanol, with a molar surface concentration that is approx. 90 times higher than the bulk concentration for both molecules. The molecular area at ML coverage (≈100 mM) was calculated to be around 32 ± 2 Å(2) per molecule for 1-pentanol and around 46 ± 2 Å(2) per molecule for 3-pentanol, which results in a higher surface concentration (molecules per cm(2)) for the linear isomer. In general we conclude therefore that isomers - with comparable surface activities - that have smaller molecular areas will be more abundant at the interface in comparison to isomers with larger molecular areas, which might be of crucial importance for the understanding of key properties of aerosols, such as evaporation and uptake capabilities as well as their reactivity.
The marked increase in occurrences of low oxygen events on continental shelves coupled with observed expansion of low oxygen regions of the ocean has drawn significant scientific and public ...attention. With this has come the need for the establishment of better definitions for widely used terms such as “hypoxia” and “dead zones”. Ocean chemists and physicists use concentration units such as
μ
molO
2
/
kg
for reporting since these units are independent of temperature, salinity and pressure and are required for mass balances and for numerical models of ocean transport. Much of the reporting of dead zone occurrences is in volumetric concentration units of mlO
2/l or mgO
2/l for historical reasons. And direct measurements of the physiological state of marine animals require reporting of the partial pressure of oxygen (pO
2) in matm or kPa since this provides the thermodynamic driving force for molecular transfer through tissue. This necessarily incorporates temperature and salinity terms and thus accommodates changes driven by climate warming and the influence of the very large temperature range around the world where oxygen limiting values are reported. Here we examine the various definitions used and boundaries set and place them within a common framework. We examine the large scale ocean pO
2 fields required for pairing with pCO
2 data for examination of the combined impacts of ocean acidification and global warming. The term “dead zones”, which recently has received considerable attention in both the scientific literature and the press, usually describes shallow, coastal regions of low oxygen caused either by coastal eutrophication and organic matter decomposition or by upwelling of low oxygen waters. While we make clear that bathyal low oxygen waters should not be confused with shallow-water “dead zones”, as deep water species are well adapted, we show that those waters represent a global vast reservoir of low oxygen water which can readily be entrained in upwelling waters and contribute to coastal hypoxia around the world and may be characterized identically. We examine the potential for expansion of those water masses onto continental shelves worldwide, thereby crossing limits set for many not adapted species.
► We propose a unified set of thresholds for “hypoxia” using consistent units. ► Partial O
2 pressure is the limiting variable: thresholds should be reported as pO
2. ► No confusion of coastal hypoxia and O
2 minimum zones: different time scales apply. ► Upwelling from O
2 minimum zones can cause coastal hypoxia: we give hot spots.
Cortical and subcortical networks have been identified that are commonly associated with attention and task engagement, along with theories regarding their functional interaction. However, a link ...between these systems has not yet been demonstrated in healthy humans, primarily because of data acquisition and analysis limitations. We recorded simultaneous EEG-fMRI while subjects performed auditory and visual oddball tasks and used these data to investigate the BOLD correlates of single-trial EEG variability at latencies spanning the trial. We focused on variability along task-relevant dimensions in the EEG for identical stimuli and then combined auditory and visual data at the subject level to spatially and temporally localize brain regions involved in endogenous attentional modulations. Specifically, we found that anterior cingulate cortex (ACC) correlates strongly with both early and late EEG components, whereas brainstem, right middle frontal gyrus (rMFG), and right orbitofrontal cortex (rOFC) correlate significantly only with late components. By orthogonalizing with respect to event-related activity, we found that variability in insula and temporoparietal junction is reflected in reaction time variability, rOFC and brainstem correlate with residual EEG variability, and ACC and rMFG are significantly correlated with both. To investigate interactions between these correlates of temporally specific EEG variability, we performed dynamic causal modeling (DCM) on the fMRI data. We found strong evidence for reciprocal effective connections between the brainstem and cortical regions. Our results support the adaptive gain theory of locus ceruleus-norepinephrine (LC-NE) function and the proposed functional relationship between the LC-NE system, right-hemisphere ventral attention network, and P300 EEG response.
Background
We analyze the long‐term outcome of surgery for Cushing's syndrome (CS) and the influence of the extent of surgical resection on the duration of postoperative cortisone substitution.
...Methods
One‐hundred forty‐one patients (129 female, 12 males; mean age: 45.7 ± 12.8 years) operated between January 2000 to June 2020 were included in the analysis. Patients suffered from manifest (124) or subclinical (17) CS due to benign unilateral adrenal neoplasia. All tumors were removed by the posterior retroperitoneoscopic approach. 105 patients had total (TA) and 36 partial (PA) adrenalectomies. All patients were discharged with ongoing corticosteroid supplementation therapy.
Results
Follow‐up data could be obtained for 83 patients. Twenty‐four (1 male, 23 females; mean age 42.3 years) underwent PA and 59 TA (6 males, 53 females; mean age 44.6 years). Mean follow‐up time was 107 ± 68 months (range: 6–243 months). The median duration of postoperative corticosteroid therapy was 9.5 months after PA and 11 months after TA (p = 0.1). Significantly, more patients after total adrenalectomy required corticosteroid therapy for more than 24 months (25% vs. 4%; p = 0.03). Recurrent ipsilateral disease occurred in one case after partial adrenalectomy and was treated by completion adrenalectomy. A case of contralateral recurrence associated with subclinical Cushing's syndrome was observed after total adrenalectomy.
Conclusions
The risk of local recurrence after partial adrenalectomy in CS is low. Cortical‐sparing surgery may shorten corticosteroid supplementation therapy after surgery.
Metachromatic leukodystrophy (MLD), a relentlessly progressive and ultimately fatal condition, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme ...arylsulfatase A (ARSA). Historically management has been palliative or supportive care. Hematopoietic stem cell transplantation is poorly effective in early-onset MLD and benefit in late-onset MLD remains controversial. Hematopoietic stem cell gene therapy, Libmeldy (atidarsagene autotemcel), was recently approved by the European Medicines Agency for early-onset MLD. Treatment benefit is mainly observed at an early disease stage, indicating the need for early diagnosis and intervention. This study contributes insights into the caregiver language used to describe initial MLD symptomatology, and thereby aims to improve communication between clinicians and families impacted by this condition and promote a faster path to diagnosis. Data was collected through a moderator-assisted online 60-min survey and 30-min semi-structured follow-up telephone interview with 31 MLD caregivers in the United States (n = 10), France (n = 10), the United Kingdom (n = 5), and Germany (n = 6). All respondents were primary caregivers of a person with late infantile (n = 20), juvenile (n = 11) or borderline late infantile/juvenile (n = 1) MLD (one caregiver reported for 2 children leading to a sample of 32 individuals with MLD). Caregivers were asked questions related to their child's initial signs and symptoms, time to diagnosis and interactions with healthcare providers. These results highlight the caregiver language used to describe the most common initial symptoms of MLD and provide added context to help elevate the index of suspicion of disease. Distinctions between caregiver descriptions of late infantile and juvenile MLD in symptom onset and disease course were also identified. This study captures the caregiver description of the physical, behavioral, and cognitive signs of MLD prior to diagnosis. The understanding of the caregiver language at symptom onset sheds light on a critical window of often missed opportunity for earlier diagnosis and therapeutic intervention in MLD.
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