Biology subjects

Lee, D. C.

Publications and source records attributed to Lee, D. C..

15 recordsLinked to original sources

bioRxiv2026

Disentangling the Crabtree and Warburg effects across syngeneic non-tumor and tumor cells.

Oxidative phosphorylation (OxPhos) and substrate-level phosphorylation (SLP) are the primary biochemical mechanisms for ATP generation in mammalian cells. Increased dependency on SLP can arise from either transient (e.g., Crabtree effect) or chronic (e.g., Warburg effect) suppression of OxPhos. We evaluated the steady-state bioenergetics of quiescent and proliferating mouse cells matched in genetic background and cell biology, including primary thioglycollate-elicited peritoneal macrophages, malignant VM-M3 glioma with macrophage characteristics, and malignant CT-2A astrocytoma. Data are presented showing: 1) OxPhos insufficiency was the primary bioenergetic hallmark of proliferating malignant cells. 2) Dysregulated proliferation was associated with lower metabolic flexibility under nutrient stress than was growth arrest or regulated proliferation. 3) The Crabtree effect was present in macrophages and involved a glucose- and time-dependent suppression of OxPhos coupled to ATP production through SLP and resistance to mitochondrial inhibitors; lowering glucose concentration or substituting glucose with respiratory fuels increased OxPhos and restored sensitivity to mitochondrial inhibitors. 4) The Warburg effect in tumor cells involved a persistent SLP dependency and resistance to mitochondrial inhibitors under equivalent glucose-replete conditions. 5) OxPhos could sustain the regulated proliferation of non-tumor cells in the absence of a Warburg effect. Collectively, our findings emphasize that comparisons between normal and cancer cell metabolism require long-term experimental endpoints that ensure steady-state ATP sufficiency.

cancer biology↗

bioRxiv2026

Integration of transcriptional signatures from brain tissue and plasma extracellular vesicles of a preclinical tauopathy mouse model

Tauopathies, including Alzheimers disease, involve progressive neurodegeneration and sustained neuroinflammation. We present a multi-compartment transcriptomic atlas of 9.6-month-old PS19 tauopathy mice compared with wild-type (WT) controls (n=8/group), profiling cortical mRNA, cortical non-coding RNA (ncRNA), and plasma small extracellular vesicle (pEV) ncRNA. In the PS19 cortex, mRNA sequencing identified 917 differentially expressed genes (DEGs), with microglial deconvolution revealing a robust transition toward disease-associated microglia (DAM) gene signature and downregulation of genes involved in oxidative phosphorylation and cholesterol biosynthesis relative to WT. Cortical ncRNA profiling identified 466 differentially expressed ncRNAs, primarily circular RNAs (circRNAs; n=331). In pEVs, 822 ncRNAs were differentially abundant, of which 657 circRNAs were identified in PS19 compared to WT mice. Cross-compartment integration demonstrated that pEV miRNA gene targets functionally mirrored genes involved in the brains inflammatory and metabolic failure. We identified a core shared signature of 33 ncRNAs, including miR-5114 (up in brain, down in pEV), circ_0008242 and circ_0002153 (up in brain and pEV), and circ_0007688 (down in brain and pEV) differentially enriched across both brain and periphery in PS19 compared to WT mice. These results demonstrate that the pEV non-coding landscape effectively tracks central tau-mediated changes in the brain transcriptional response. This study identifies circRNAs as the most numerically perturbed ncRNA class and provides a foundation for non-invasive biomarker development in tauopathy.

neuroscience↗

bioRxiv2025

Tau pathology reprograms glucose metabolism to support glutamatergic activity and excitatory imbalance

Alzheimers disease (AD) is not only characterized by amyloid-beta (A{beta}) and tau pathology, but also by early and progressive disruptions in metabolism. Neuronal excitability is tightly coupled with metabolic demand, and aberrant excitatory activity - observed in AD patients and models - can drive changes in metabolism. While A{beta}-related metabolic impairments are well-described, less is known about how tau pathology independently contributes to altered metabolic states and excitatory tone. Therefore, we explored how tau pathology impacted whole body and CNS metabolism in mouse models of tauopathy, including the P301S PS19 and Tau4RTg2652 mice. In both models, hyperphosphorylated tau prevents the age-related decline in whole-body metabolism by preserving glucose tolerance and mitigating shifts in fuel utilization (respiratory exchange ratio; RER), suggesting the mice are "glucose needy". Tau pathology also preserves diurnal rhythms in hippocampal interstitial fluid (ISF) glucose and lactate, likely due to increased neuronal activity during the active (dark) phase. Stable isotope-resolved metabolomics following 13C-glucose administration revealed that glucose is preferentially shunted toward glutamate synthesis--at the expense of GABA--highlighting a shift in excitatory/inhibitory balance. Interestingly, these changes were not explained by a primary deficit in synaptic mitochondria but by alterations in glycolytic flux. Adaptations were time of day dependent, where ISF glutamate rises after a glucose injection in the dark period but not the light period. This suggests increased glutamatergic activity may drive metabolic demand during the dark period when mice are more active. Together, these studies fundamentally highlight the important coupling between metabolism and excitability, which is disrupted by hyperphosphorylated tau, tau aggregation, and neurodegeneration. Understanding how tau pathology and metabolism interrelate provides a novel lens for the development of therapeutic targets in late stage AD.

neuroscience↗

bioRxiv2025

Lactate cannot replace glucose for maintaining the viability of mouse and human glioma cells

ObjectivesAerobic lactic acid fermentation (the "Warburg effect") is associated with OxPhos insufficiency and altered energy metabolism in most cancers. Whether lactate is a major fuel in cancer cells remains debated. This study investigated whether lactate could serve as a metabolic fuel in glioma cells and replace glucose to support viability. MethodsA bioluminescence ATP assay and calcein-AM/EthD-III double-staining were used to measure ATP content and viability in mouse (VM-M3, CT-2A) and human (U-87MG) glioma cells differing in cell biology and genetic background. Viability was assessed in thioglycollate-elicited peritoneal macrophages (TPMs) from VM/Dk and C57BL/6J mice, used as syngeneic non-neoplastic controls for VM-M3 and CT-2A gliomas, respectively. Oxygen consumption rate (OCR) was determined using the Resipher system. ResultsLactate alone failed to sustain ATP content and viability in all glioma cell lines. ATP content and viability were lower in cancer cells cultured in glutamine and lactate than in glucose and glutamine. In contrast, lactate alone sustained over 45% viability in both TPM models. Moreover, viability was similar between TPMs cultured in glutamine and lactate and in glucose and glutamine. In human U-87MG, lactate addition under severe glucose restriction increased OCR and viability. A low dose of the glycolysis inhibitor 2-deoxy-D-glucose abolished both increases. ConclusionsOur results suggest non-neoplastic mouse TPMs utilize lactate more effectively than mouse glioma cells. In U-87MG, lactate utilization appears glycolysis-dependent, given its sensitivity to 2-deoxy-D-glucose. In conclusion, our data does not support lactate as a major oxidative fuel for viability in mouse and human glioma cells.

cancer biology↗

bioRxiv2025

The differential effect of glutamine supplementation on the orthotopic and subcutaneous growth of two syngeneic murine models of glioma

Glutamine serves as a major fuel source for tumor cell proliferation while simultaneously playing an essential role in maintaining gastrointestinal health and immune function. Controversy exists regarding glutamine supplementation for cancer patients undergoing chemotherapy and radiation, with concerns that it may stimulate cancer growth. The present study is the first to examine the effects of dietary glutamine supplementation (0.4g/kg/day) on the growth of malignant gliomas, which utilize large amounts of glutamine to satisfy metabolic demands. Brain bioluminescence and subcutaneous tumor volumes were used to assess the influence of glutamine supplementation on the growth of the syngeneic VM-M3 and CT-2A preclinical models of glioma. Glutamine supplementation had no significant effect on the orthotopic growth of the VM-M3 or the CT-2A gliomas when compared to non-supplemented controls. However, glutamine supplementation significantly increased tumor volume by 28% in the VM-M3 and by 166% in the CT-2A tumors when grown subcutaneously outside the central nervous system (CNS) relative to controls. Additionally, glutamine supplementation increased serum glutamine despite a localized decrease in intratumoral glutamine concentrations. Caution is warranted when considering glutamine supplementation in patients with glutamine-dependent malignancies. Further studies are needed to better understand the potential risks and benefits of glutamine supplementation in cancer therapy.

cancer biology↗

bioRxiv2025

Citrullination of TDP-43 is a key post-translation modification associated with structural and functional changes and progressive pathology in TDP-43 mouse models and human proteinopathies

TAR DNA-binding protein 43 (TDP-43) pathology is associated with a spectrum of clinical dementias including limbic-predominant age-related TDP-43 encephalopathy neuropathological changes (LATE-NC). Post-translational modifications (PTM) are linked to TDP-43 toxic gain-of-function and cytoplasmic aggregation1-3. Phosphorylation remains the most investigated PTM and a standard criterion for determining pathology progression and clinical subclassification in TDP-43 proteinopathies4-7. However, full spectrum of PTMs on TDP-43 structure and biology remain unknown. Utilizing mass-spectrometry analysis we identified citrullination as a novel and irreversible "bona-fide" PTM of TDP-43 protein. We recognized peptidyl arginine deiminase 2 and 4 (PAD2 and PAD4) to mediate the conversion of arginine (R) to citrulline (citR) in vitro and demonstrated increased PAD2 and PAD4 expression and TDP-43 citrullination in a human wildtype TDP-43 mouse model (Tg (Thy1-TARDBP4). Transmission electron microscopy imaging analysis revealed citrullination induced vast structural changes while ThT analysis demonstrated altered aggregation kinetics of citrullinated (citR) TDP-43 protein. We further provided mechanistic evidence on reduced electrostatic and pi-pi interactions of citR TDP-43 Low Complexity Domain (LCD) with RNA, favoring liquid-solid phase separation and condensate formation. Generation and validation of several citR TDP-43 specific antibodies against several TDP-43 epitopes revealed epitope and domain-specific effects of citrullination on TDP-43 solubility in vivo. Importantly, we found distinct reactivities of citR TDP-43 antibodies shedding light into the contribution of epitope-specific properties of human citR TDP-43 to novel pathological citR TDP-43 assemblies in human brain tissue from LATE-NC, with or without comorbid Alzheimers disease neuropathologic changes (ADNC). These findings provided a unique look into the temporal citR TDP-43 signatures, and the potential clinical relevance associated with progression of pure LATE-NC and comorbid ADNC + LATE-NC. Collectively, these data reveal the existence of irreversible TDP-43 citrullination at targeted sites via induced PAD2/PAD4 activities, presenting a critical step in TDP-43 proteinopathy.

neuroscience↗

bioRxiv2024

Probing tau citrullination in Alzheimer's disease brains and mouse models of tauopathy

Tauopathies, which include Alzheimers disease (AD) share a common defining factor, namely misfolded tau protein. However, the "upstream" etiology and downstream clinical manifestations of tauopathies are quite diverse. Tau deposition elicits different pathological phenotypes and outcomes depending on the tau strain and regional susceptibility. Posttranslational modifications (PTM) can alter tau structure, function, networks, and its pathological sequalae. We uncovered a novel PTM of tau, named citrullination, caused by peptidyl arginine deiminase (PAD) enzymes. PAD induced citrullination irreversibly converts arginine residues to citrulline, producing net loss of positive charge, elimination of pi-pi interactions, and increased hydrophobicity. We observed increased PAD2 and PAD4 in Alzheimers disease (AD) brain and that they both can citrullinate tau. Tau can become citrullinated by PADs at all 14 arginine residues throughout the N-terminal domain (N-term), proline-rich domain (PR), microtubule binding repeat domain (MBR), and C-terminal domain (C-term) on full length tau (2N4R). Citrullination of tau impacts fibrillization and oligomerization rates in aggregation assays. Utilizing a panel of novel citrullinated tau (citR tau) antibodies, we identified citrullination of tau in vitro, several animal models of tauopathies, and Alzheimers disease (AD). CitR tau increased with Braak stage and was enriched in AD brains with higher phospho-tau burden. This work provides a new area of tau biology that signifies further consideration in the emerging spectrum of tauopathies and its clinical understanding.

neuroscience↗

bioRxiv2024

Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells

Energy is necessary for tumor cell viability and growth. Aerobic glucose-driven lactic acid fermentation is a common metabolic phenotype seen in most cancers including malignant gliomas. This metabolic phenotype is linked to abnormalities in mitochondrial structure and function. A luciferin-luciferase bioluminescence ATP assay was used to measure the influence of amino acids, glucose, and oxygen on ATP content and viability in mouse (VM-M3 and CT-2A) and human (U-87MG) glioma cells that differed in cell biology, genetic background, and species origin. Oxygen consumption was measured using the Resipher system. Extracellular lactate and succinate were measured as end products of the glycolysis and glutaminolysis pathways, respectively. The results showed that: 1) glutamine was a source of ATP content irrespective of oxygen. No other amino acid could replace glutamine in sustaining ATP content and viability; 2) ATP content persisted in the absence of glucose and under hypoxia, ruling out substantial contribution through either glycolysis or oxidative phosphorylation (OxPhos) under these conditions; 3) Mitochondrial complex IV inhibition showed that oxygen consumption was not an accurate measure for ATP production through OxPhos. The glutaminase inhibitor, 6-diazo-5-oxo-L-norleucine (DON), reduced ATP content and succinate export in cells grown in glutamine. The data suggests that mitochondrial substrate level phosphorylation in the glutamine-driven glutaminolysis pathway contributes to ATP content in these glioma cells. A new model is presented highlighting the synergistic interaction between the high-throughput glycolysis and glutaminolysis pathways that drive malignant glioma growth and maintain ATP content through the aerobic fermentation of both glucose and glutamine. Summary statementMalignant gliomas, regardless of cell of origin or species, rely on fermentation mechanisms for ATP production due to OxPhos insufficiency. Glucose and glutamine together are necessary and sufficient for dysregulated tumor cell growth, whereas OxPhos is neither necessary nor sufficient.

cancer biology↗

bioRxiv2024

Nutrient Sensing Receptor GPRC6A Regulates mTORC1 Signaling and Tau Biology

Tauopathies, including Alzheimers disease (AD), comprise microtubule-associated protein tau aggregates that cause neuronal cell death and clinical cognitive decline. Reducing overall tau abundance remains a central strategy for therapeutics; however, no disease-modifying treatment exists to date. One principal pathway for balancing cellular proteostasis includes the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Recently, arginine emerged as one of the primary amino acids to activate mTORC1 through several intracellular arginine sensors and an extracellular arginine receptor, namely the G protein-coupled receptor (GPCR) family C, group 6, member A (GPRC6A). Human AD brains were previously reported with elevated mTORC1 signaling; however, it is unclear whether arginine sensing and signaling to mTORC1 plays a role in tauopathies. Herein, we examined arginine sensing associated with mTORC1 signaling in the human AD and animal models of tauopathy. We found that human AD brains maintained elevated levels of arginine sensors with potential uncoupling of arginine sensing pathways. Furthermore, we observed increased GPRC6A and arginine in the brain, accompanied by increased mTORC1 signaling and decreased autophagy in a mouse model of tauopathy (Tau PS19). We also discovered that both supplementing arginine and overexpressing GPRC6A in cell culture models could independently activate mTORC1 and promote tau accumulation. In addition, we found that suppressing GPRC6A signaling by either genetic reduction or pharmacological antagonism reduced tau accumulation, phosphorylation, and oligomerization. Overall, these findings uncover the crucial role of arginine sensing pathways in deregulating mTORC1 signaling in tauopathies and identify GPRC6A as a promising target for future therapeutics in tauopathies and other proteinopathies. Significance StatementTauopathies, including Alzheimers disease (AD), accumulate pathogenic tau protein inclusions that potentially contribute to the hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling and eventually cause neuronal cell death. Here, we presented novel findings that AD and animal models of tauopathy maintained increased expression of arginine sensors and uncoupling of arginine sensing associated with mTORC1 signaling. We investigated the role of a putative extracellular arginine and basic L-amino acid sensing G protein-coupled receptor (GPCR) family C, group 6, member A (GPRC6A) in activating mTORC1 and accelerating pathogenic tau phenotypes in several cell models. Additionally, we showed that genetic repression or antagonism of GPRC6A signaling provides a novel therapeutic target for tauopathies and other proteinopathies.

neuroscience↗

bioRxiv2024

Identification of retinal tau oligomers, citrullinated tau, and other tau isoforms in early and advanced AD and relations to disease status

ImportanceThis study identifies and quantifies diverse pathological tau isoforms in the retina of both early and advanced-stage Alzheimers disease (AD) and determines their relationship with disease status. ObjectiveA case-control study was conducted to investigate the accumulation of retinal neurofibrillary tangles (NFTs), paired helical filament (PHF)-tau, oligomeric tau (oligo-tau), hyperphosphorylated tau (p-tau), and citrullinated tau (Cit-tau) in relation to the respective brain pathology and cognitive dysfunction in mild cognitively impaired (MCI) and AD dementia patients versus normal cognition (NC) controls. Design, setting and participantsEyes and brains from donors diagnosed with AD, MCI (due to AD), and NC were collected (n=75 in total), along with clinical and neuropathological data. Brain and retinal cross-sections-in predefined superior-temporal and inferior-temporal (ST/IT) subregions-were subjected to histopathology analysis or Nanostring GeoMx digital spatial profiling. Main outcomes and measureRetinal burden of NFTs (pretangles and mature tangles), PHF-tau, p-tau, oligo-tau, and Cit-tau was assessed in MCI and AD versus NC retinas. Pairwise correlations revealed associations between retinal and brain parameters and cognitive status. ResultsIncreased retinal NFTs (1.8-fold, p=0.0494), PHF-tau (2.3-fold, p<0.0001), oligo-tau (9.1-fold, p<0.0001), CitR209-tau (4.3-fold, p<0.0001), pSer202/Thr205-tau (AT8; 4.1-fold, p<0.0001), and pSer396-tau (2.8-fold, p=0.0015) were detected in AD patients. Retinas from MCI patients showed significant increases in NFTs (2.0-fold, p=0.0444), CitR209-tau (3.5-fold, p=0.0201), pSer396-tau (2.6-fold, p=0.0409), and, moreover, oligo-tau (5.8-fold, p=0.0045). Nanostring GeoMx quantification demonstrated upregulated retinal p-tau levels in MCI patients at phosphorylation sites of Ser214 (2.3-fold, p=0.0060), Ser396 (1.8-fold, p=0.0052), Ser404 (2.4-fold, p=0.0018), and Thr231 (3.3-fold, p=0.0028). Strong correlations were found between retinal tau forms to paired-brain pathology and cognitive status: a) retinal oligo-tau vs. Braak stage (r=0.60, P=0.0002), b) retinal PHF-tau vs. ABC average score (r=0.64, P=0.0043), c) retinal pSer396-tau vs. brain NFTs (r=0.68, P<0.0001), and d) retinal pSer202/Thr205-tau vs. MMSE scores (r= -0.77, P=0.0089). Conclusions and RelevanceThis study reveals increases in immature and mature retinal tau isoforms in MCI and AD patients, highlighting their relationship with brain pathology and cognition. The data provide strong incentive to further explore retinal tauopathy markers that may be useful for early detection and monitoring of AD staging through noninvasive retinal imaging.

pathology↗

bioRxiv2023

Effect of Water Fluoridation on VM-M3 Tumor Metastasis

Water fluoridation has been used for combatting dental caries in the general population. Although fluoride has been evaluated as a possible carcinogen, no studies have evaluated the influence of water fluoridation on tumor metastasis. Ex vivo bioluminescent imaging and tumor volume measurements were used to assess the influence of water fluoridation on the metastatic spread of VM-M3/Fluc tumor cells grown in their syngeneic inbred VM/Dk mice that received either sodium fluoride (NaF) or hydrofluorosilicic acid (HFSA) in the drinking water (at either 5.0 mg/L or 20.0 mg/L) for 35 days. During the course of the study, there was no difference in water intake or body weight between the control mice and mice that drank either NaF or HFSA. No significant differences were found for VM-M3/Fluc organ metastasis in the mice that drank water with either 5.0 mg/L or 20.0 mg/L NaF or HFSA versus control mice that drank water without fluoride. Both overall survival and flank tumor volumes were similar in control mice and in mice that drank water containing HFSA. In conclusion, the results showed that fluoride present in the drinking water had no statistically significant effect on the metastatic spread of VM-M3/Fluc tumor cells nor on mouse survival.

cancer biology↗

bioRxiv2022

Recombinant Origin and Interspecies Transmission of a HERV-K(HML-2)-related Primate Retrovirus 1 With a Novel RNA Transport Element

HERV-K(HML-2), the youngest clade of human endogenous retroviruses (HERVs), includes many intact or nearly intact proviruses, but no replication competent HML-2 proviruses have been identified in humans. HML-2-related proviruses are present in other primates, including rhesus macaques, but the extent and timing of HML-2 activity in macaques remains unclear. We have identified 145 HML-2-like proviruses in rhesus macaques, including a clade of young, rhesus-specific insertions. Age estimates, intact ORFs, and insertional polymorphism of these insertions are consistent with recent or ongoing infectious activity in macaques. 108 of the proviruses form a clade characterized by an ~750 bp sequence between env and the 3 LTR, derived from an ancient recombination with a HERV-K(HML-8)-related virus. This clade is found in Old World monkeys (OWM), but not great apes, suggesting it originated after the ape/OWM split. We identified similar proviruses in white-cheeked gibbons; the gibbon insertions cluster within the OWM recombinant clade, suggesting interspecies transmission from OWM to gibbons. The LTRs of the youngest proviruses have deletions in U3, which disrupt the Rec Response Element (RcRE), required for nuclear export of unspliced viral RNA. We show that the HML-8 derived region functions as a Rec-independent constitutive transport element (CTE), indicating the ancestral Rec-RcRE export system was replaced by a CTE mechanism.

microbiology↗

bioRxiv2021

Population assessment and habitat associations of the Visayan Hornbill Penelopides panini in Northwest Panay, Philippines

BackgroundSeven out of 10 hornbill species in the Philippines are threatened with extinction. Among these is the Endangered Visayan hornbill Penelopides panini, found on Panay and Negros islands. Threatened by habitat loss and hunting, its population size is thought to have declined from 1,800 individuals 20 years ago to less than 1,000. However, a recent study on Negros estimated 3,564 individuals across three core forest blocks. This study aims to quantify the Visayan hornbill population size in and around the Northwest Panay Peninsula Natural Park (NWPPNP) on Panay, the largest contiguous low-elevation forest landscape remaining across its range, and its broad habitat associations across a gradient of environmental degradation. MethodsHornbills were surveyed using 10-minute Distance sampling point counts (n = 362) along transects (average length 1.1 km). Habitat variables were recorded, while habitat was classified into: primary forest, secondary forest, plantation or open habitat. Using Distance software, population densities were estimated for, and post-stratified by habitat, with the overall population estimate taken as a mean of habitat density estimates weighted by habitat area. Using logistic binary regression, hornbill occurrence was modelled against reduced habitat factors extracted from factor analysis of the habitat data. ResultsSurveys covered 204.4 km2 of the 374.8 km2 Northwest Panay Peninsula. Hornbills were not recorded in plantation or open habitats. The estimated density of hornbills was significantly higher in primary forest (17.7 individuals km-2 {+/-} 29.7% CV) than in secondary forest (5.0 individuals km-2 {+/-} 36.7 %CV; z = 9.538, P < 0.001). The overall population estimate is 2,231 individuals {+/-} 24.4 %CV for the NWPPNP and environs, and 2,949 individuals {+/-} 23.1 %CV for the entire Northwest Panay Peninsula. One habitat factor, described by increasing numbers of large trees, elevation and distance from the Parks boundary, had a significant positive effect in explaining hornbill occurrence, with hornbills significantly more likely to occur in primary forest than the other habitat types. ConclusionsOur study demonstrates the habitat preference of the Visayan hornbill, highlights the importance of the NWPPNP for the species conservation, and provides strong evidence for re-assessing the global population size.

ecology↗

bioRxiv2021

Trade-driven trapping dampens the biodiversity benefits of forest restoration in Southeast Asia

Tropical forest restoration stands to deliver important conservation gains, particularly in lowland Southeast Asia, which has suffered some of the worlds highest rates of forest loss and degradation. This promise, however, depends on the extent to which biodiversity at forest restoration sites continues to be exposed to threats. A key knowledge gap concerns the extent to which biodiversity recovery in naturally regenerating tropical forests is impacted by trapping for the multi-million-dollar wildlife trade. Here, we use a repeated survey dataset to quantify rates of avian community recovery under forest regeneration, at a flagship restoration site in the lowland rainforests of Sumatra, Indonesia. We show that over a decade, forest regeneration was associated with significant abundance increases for 43.8% of bird species. However, the apparent negative impacts of trade-driven trapping on avian populations also intensified: the proportion of species that show increased abundance only in very remote forests increased from 5.4% to 16.2%, while the overall accessibility of the forest increased. We found that 14% of species did not recover as fast as predicted based on the observed improvement in forest conditions over the study period. Our results highlight the potential for rapid avifaunal recovery in regenerating tropical forests, but also emphasize the urgency of tackling the serious threat of wildlife trade to Southeast Asias biodiversity.

ecology↗

bioRxiv2017

Does tobacco abstinence decrease reward sensitivity? A human laboratory test

IntroductionAnimal studies report abstinence from nicotine makes rewards less rewarding; however, the results of human tests of the effects of cessation on reward sensitivity are mixed. The current study tested reward sensitivity in abstinent smokers using more rigorous methods than most prior studies.\n\nMethodsA human laboratory study compared outcomes for 1 week prior to quitting to those during 4 weeks post-quit. The study used smokers trying to quit, objective and subjective measures, multiple measures during smoking and abstinence, and monetary rewards to increase the prevalence of abstinence. Current daily smokers (n = 211) who were trying to quit completed an operant measure of reward sensitivity and a survey of pleasure from various rewards as well as self-reports of anhedonia, delay discounting, positive affect and tobacco withdrawal twice each week. A comparison group of long-term former smokers (n = 67) also completed the tasks weekly for 4 weeks. Primary analyses were based on the 61 current smokers who abstained for all 4 weeks.\n\nResultsStopping smoking decreased self-reported pleasure from rewards but did not decrease reward sensitivity on the operant task. Abstinence also decreased self-reported reward frequency and increased the two anhedonia measures. However, the changes with abstinence were small for all outcomes (6-14%) and most lasted less than a week.\n\nConclusionAbstinence from tobacco decreased most self-report measures of reward sensitivity; however, it did not change the objective measure. The self-report effects were small.\n\nImplicationsO_LIAnimal research suggests that nicotine withdrawal decreases reward sensitivity. Replication tests of this in humans have produced inconsistent results.\nC_LIO_LIWe report what we believe is a more rigorous test\nC_LIO_LIWe found smoking abstinence slightly decreases self-reports of reward sensitivity but does not do so for behavioral measures of reward sensitivity\nC_LI

neuroscience↗