Generally unseen and infrequently measured, submarine groundwater discharge (SGD) can transport potentially large loads of nutrients and other land-based contaminants to coastal ecosystems. To ...examine this linkage we employed algal bioassays, benthic community analysis, and geochemical methods to examine water quality and community parameters of nearshore reefs adjacent to a variety of potential, land-based nutrient sources on Maui. Three common reef algae, Acanthophora spicifera, Hypnea musciformis, and Ulva spp. were collected and/or deployed at six locations with SGD. Algal tissue nitrogen (N) parameters (δ15N, N %, and C:N) were compared with nutrient and δ15N-nitrate values of coastal groundwater and nearshore surface water at all locations. Benthic community composition was estimated for ten 10-m transects per location. Reefs adjacent to sugarcane farms had the greatest abundance of macroalgae, low species diversity, and the highest concentrations of N in algal tissues, coastal groundwater, and marine surface waters compared to locations with low anthropogenic impact. Based on δ15N values of algal tissues, we estimate ca. 0.31 km2 of Kahului Bay is impacted by effluent injected underground at the Kahului Wastewater Reclamation Facility (WRF); this region is barren of corals and almost entirely dominated by colonial zoanthids. Significant correlations among parameters of algal tissue N with adjacent surface and coastal groundwater N indicate that these bioassays provided a useful measure of nutrient source and loading. A conceptual model that uses Ulva spp. tissue δ15N and N % to identify potential N source(s) and relative N loading is proposed for Hawai'i. These results indicate that SGD can be a significant transport pathway for land-based nutrients with important biogeochemical and ecological implications in tropical, oceanic islands.
When O2 is plentiful, the mitochondrial electron transport chain uses it as a terminal electron acceptor. However, the mammalian retina thrives in a hypoxic niche in the eye. We find that ...mitochondria in retinas adapt to their hypoxic environment by reversing the succinate dehydrogenase reaction to use fumarate to accept electrons instead of O2. Reverse succinate dehydrogenase activity produces succinate and is enhanced by hypoxia-induced downregulation of cytochrome oxidase. Retinas can export the succinate they produce to the neighboring O2-rich retinal pigment epithelium-choroid complex. There, succinate enhances O2 consumption by severalfold. Malate made from succinate in the pigment epithelium can then be imported into the retina, where it is converted to fumarate to again accept electrons in the reverse succinate dehydrogenase reaction. This malate-succinate shuttle can sustain these two tissues by transferring reducing power from an O2-poor tissue (retina) to an O2-rich one (retinal pigment epithelium-choroid).
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•Succinate is produced by reversal of succinate dehydrogenase in the retina•Hypoxia decreases complex IV expression to drive retinal succinate production•The retina exports succinate, which is oxidized by the RPE-choroid•The RPE-choroid exports malate, which fuels retinal succinate production
Bisbach et al. describe a metabolite shuttle that can transfer electrons from a hypoxic tissue to an O2-rich one. In the retina, low O2 causes succinate dehydrogenase to operate in reverse, reducing fumarate to produce succinate. Retinas export this succinate, and the O2-rich RPE-choroid imports and oxidizes it.
People make social inferences without intentions, awareness, or effort, i.e., spontaneously. We review recent findings on spontaneous social inferences (especially traits, goals, and causes) and ...closely related phenomena. We then describe current thinking on some of the most relevant processes, implicit knowledge, and theories. These include automatic and controlled processes and their interplay; embodied cognition, including mimicry; and associative versus rule-based processes. Implicit knowledge includes adult folk theories, conditions of personhood, self-knowledge to simulate others, and cultural and social class differences. Implicit theories concern Bayesian networks, recent attribution research, and questions about the utility of the disposition-situation dichotomy. Developmental research provides new insights. Spontaneous social inferences include a growing array of phenomena, but they have been insufficiently linked to other phenomena and theories. We hope the links suggested in this review begin to remedy this.
In observational studies, type-2 diabetes (T2D) is associated with an increased risk of coronary heart disease (CHD), yet interventional trials have shown no clear effect of glucose-lowering on CHD. ...Confounding may have therefore influenced these observational estimates. Here we use Mendelian randomization to obtain unconfounded estimates of the influence of T2D and fasting glucose (FG) on CHD risk. Using multiple genetic variants associated with T2D and FG, we find that risk of T2D increases CHD risk (odds ratio (OR)=1.11 (1.05-1.17), per unit increase in odds of T2D, P=8.8 × 10(-5); using data from 34,840/114,981 T2D cases/controls and 63,746/130,681 CHD cases/controls). FG in non-diabetic individuals tends to increase CHD risk (OR=1.15 (1.00-1.32), per mmol·per l, P=0.05; 133,010 non-diabetic individuals and 63,746/130,681 CHD cases/controls). These findings provide evidence supporting a causal relationship between T2D and CHD and suggest that long-term trials may be required to discern the effects of T2D therapies on CHD risk.
Summary Few studies are available to inform duration of intravenous antibiotics for children and when it is safe and appropriate to switch to oral antibiotics. We have systematically reviewed ...antibiotic duration and timing of intravenous to oral switch for 36 paediatric infectious diseases and developed evidence-graded recommendations on the basis of the review, guidelines, and expert consensus. We searched databases and obtained information from references identified and relevant guidelines. All eligible studies were assessed for quality. 4090 articles were identified and 170 studies were included. Evidence relating antibiotic duration to outcomes in children for some infections was supported by meta-analyses or randomised controlled trials; in other infections data were from retrospective series only. Criteria for intravenous to oral switch commonly included defervescence and clinical improvement with or without improvement in laboratory markers. Evidence suggests that intravenous to oral switch can occur earlier than previously recommended for some infections. We have synthesised recommendations for antibiotic duration and intravenous to oral switch to support clinical decision making and prospective research.
Abstract
Rods and cones use intracellular Ca
2+
to regulate many functions, including phototransduction and neurotransmission. The Mitochondrial Calcium Uniporter (MCU) complex is thought to be the ...primary pathway for Ca
2+
entry into mitochondria in eukaryotes. We investigate the hypothesis that mitochondrial Ca
2+
uptake via MCU influences phototransduction and energy metabolism in photoreceptors using a
mcu
-/-
zebrafish and a rod photoreceptor-specific
Mcu
-/-
mouse. Using genetically encoded Ca
2+
sensors to directly examine Ca
2+
uptake in zebrafish cone mitochondria, we found that loss of MCU reduces but does not eliminate mitochondrial Ca
2+
uptake. Loss of MCU does not lead to photoreceptor degeneration, mildly affects mitochondrial metabolism, and does not alter physiological responses to light, even in the absence of the Na
+
/Ca
2+
, K
+
exchanger. Our results reveal that MCU is dispensable for vertebrate photoreceptor function, consistent with its low expression and the presence of an alternative pathway for Ca
2+
uptake into photoreceptor mitochondria.
When O
is plentiful, the mitochondrial electron transport chain uses it as a terminal electron acceptor. However, the mammalian retina thrives in a hypoxic niche in the eye. We find that mitochondria ...in retinas adapt to their hypoxic environment by reversing the succinate dehydrogenase reaction to use fumarate to accept electrons instead of O
. Reverse succinate dehydrogenase activity produces succinate and is enhanced by hypoxia-induced downregulation of cytochrome oxidase. Retinas can export the succinate they produce to the neighboring O
-rich retinal pigment epithelium-choroid complex. There, succinate enhances O
consumption by severalfold. Malate made from succinate in the pigment epithelium can then be imported into the retina, where it is converted to fumarate to again accept electrons in the reverse succinate dehydrogenase reaction. This malate-succinate shuttle can sustain these two tissues by transferring reducing power from an O
-poor tissue (retina) to an O
-rich one (retinal pigment epithelium-choroid).
Photoreceptors are specialized neurons that rely on Ca2+ to regulate phototransduction and neurotransmission. Photoreceptor dysfunction and degeneration occur when intracellular Ca2+ homeostasis is ...disrupted. Ca2+ homeostasis is maintained partly by mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU), which can influence cytosolic Ca2+ signals, stimulate energy production, and trigger apoptosis. Here we discovered that zebrafish cone photoreceptors express unusually low levels of MCU. We expected that this would be important to prevent mitochondrial Ca2+ overload and consequent cone degeneration. To test this hypothesis, we generated a cone-specific model of MCU overexpression. Surprisingly, we found that cones tolerate MCU overexpression, surviving elevated mitochondrial Ca2+ and disruptions to mitochondrial ultrastructure until late adulthood. We exploited the survival of MCU overexpressing cones to additionally demonstrate that mitochondrial Ca2+ uptake alters the distributions of citric acid cycle intermediates and accelerates recovery kinetics of the cone response to light. Cones adapt to mitochondrial Ca2+ stress by decreasing MICU3, an enhancer of MCU-mediated Ca2+ uptake, and selectively transporting damaged mitochondria away from the ellipsoid toward the synapse. Our findings demonstrate how mitochondrial Ca2+ can influence physiological and metabolic processes in cones and highlight the remarkable ability of cone photoreceptors to adapt to mitochondrial stress.
Background
Incorporation of patient-reported outcomes such as health-related quality of life has become increasingly important in the management of chronic diseases such as cancer. In this ...prospective study, we examined the effect of surgical resection on quality of life in patients with intestinal and pancreatic neuroendocrine tumors (NETs).
Methods
Thirty-two patients underwent NET resection at our institution from January 2020 to January 2022. All patients completed the 12-item short-form quality-of-life survey prior to surgery, as well as at the 3-, 6-, and 12-month postoperative time points. The presence and severity of specific carcinoid syndrome symptoms (diarrhea, flushing, and abdominal pain) were also recorded during pre- and postoperative appointments.
Results
Patients experienced significant increases in both mental and physical health after surgery. Mental health scores significantly increased at all three time points (baseline: 51.33; 3-month: 53.17,
p
= 0.02; 6-month: 57.20,
p
< 0.001; 12-month: 57.34,
p
= 0.002), and physical health scores increased at 6 and 12 months (baseline: 50.39; 6-month: 53.16,
p
= 0.04; 12-month: 55.02,
p
= 0.003). Younger patients benefited more in terms of physical health, while older patients had more significant increases in mental health. Patients with metastatic disease, larger primary tumors, and those receiving medical therapy had lower baseline quality-of-life scores and greater improvements after surgery. The vast majority of patients in this study also experienced alleviation of carcinoid syndrome symptoms.
Conclusions
In addition to prolonging survival, resection of intestinal and pancreatic NETs leads to significantly improved patient-reported quality of life.
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