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Fanconi-Bickel syndrome is a rare metabolic disorder caused by decreased glucose transporter 2 (GLUT2) function due to several known mutations in the SLC2A2 gene. As of 2020, 144 cases of FBS had been described in the literature. Metabolic and somatic sequelae include dysglycemia and accumulation of glycogen in the kidney and liver. However, there are no descriptions in the literature of possible neuropsychiatric manifestations of FBS. This case report is to our knowledge the first in this regard, describing a patient with Fanconi Bickel syndrome who was admitted to our psychiatric inpatient unit while experiencing acute mania. We conceptualize the case as a novel psychiatric presentation of acute mania in Fanconi Bickel syndrome, which may inform our understanding of bipolar disorder pathophysiology because of the hypothesized functional changes in neural pathways involving the paraventricular thalamus induced by decreased GLUT2 activity in FBS.

Therapeutic options for stage III non-small-cell lung cancer (NSCLC) consist of definitive chemoradiation, surgery combined with neoadjuvant/adjuvant chemotherapy, and trimodality therapy. More recently, biologically driven systemic therapy options, including immunotherapy and targeted therapy, have become increasingly available.A customized, case-based survey was designed and distributed to members of the International Association for the Study of Lung Cancer (IASLC) to determine practice habits and preferences for NSCLC patients with stage III disease and N2 to N3 nodal involvement.Data were compiled from 87 respondents from 31 countries, including medical oncologists (49%), surgical oncologists (24%), and radiation oncologists (21%). Definitive chemoradiation was more likely to be recommended for stage IIIC (98.2%) or stage IIIB (75.8%) scenarios compared with stage IIIA (59.6%) without actionable driver alterations (P.0001 and .0003, respectively); and chemoradiation was more likely for stage IIIB (57.7%) compared to stage IIIA (39.9%) with actionable EGFR/ALK alterations (P = .008). Surgery was more likely to be recommended in the presence of an actionable alteration (38.7% vs. 19%, P.0001). Surgeons were more likely than medical oncologists to recommend surgical approaches in scenarios without actionable alterations (25.6% vs. 11.2%, P.0001) or with actionable alterations (57.5% vs. 31.1%, P = .0001).The dominant recommended strategy for stage III NSCLC was chemoradiation, although respondents were more likely to recommend surgical approaches in the presence of actionable alterations. Despite the lack of reported clinical trial data, many IASLC lung cancer experts favored targeted therapy when actionable driver alterations were present.

Equilibration of phospholipids between the two monolayers of the lipid bilayer of cellular membranes is mediated by scramblases acting as phospholipid shuttling proteins that are critical for cellular function, particularly during inter-organelle contact. Recent work has identified several protein scramblases, including TMEM41B, VMP1 and ATG9 that are critical in autophagy. More recently, ATG9, TMEM41B, and VMP1 have also been discovered to be important regulators of cellular lipid homeostasis. In vivo mouse models involving ablation of TMEM41B in liver have shown that knockout of these proteins can lead to rapid development of non-alcoholic steatohepatitis (NASH) and systemic dyslipidemia, though this has not been explored yet with ATG9. The resulting phenotype is likely due to the combined effects of a severe lipid secretion defect caused by stalled neutral lipids export from the endoplasmic reticulum (ER) membrane bilayer coupled with increased lipogenesis. Here we briefly discuss recent exciting findings on the topic of scramblases in autophagy, their relevance to human non-alcoholic fatty liver disease (NAFLD)/NASH, as well as future directions in this research.

Alcohol-related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the primary causes of chronic liver disease in western countries. Liver transplantation is currently one of the most efficient approaches to save patients with liver failure, which is often associated with hepatic ischemia-reperfusion (IR) injury. IR injury is exacerbated by hepatic steatosis, yet the mechanism remains elusive. Necroptosis is a form of regulated cell death mediated by receptor-interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like (MLKL) protein, which has been implicated in the pathogenesis of ALD and NAFLD. Though necroptosis plays an important role in IR injury of high fat diet - induced steatotic livers, the role of necroptosis in IR injury of ethanol - induced steototic livers has not been investigated. In the present study, we used chronic plus binge alcohol (Gao-binge) feeding followed by IR surgery to investigate IR liver injury with ethanol-associated steatosis. We found that the levels of key necroptotic proteins MLKL and RIP3 increased in alcohol-fed mouse livers. Moreover, we observed increased liver injury after IR in control diet-fed mice, which was further exacerbated by alcohol feeding based on serum alanine aminotransferase (ALT) levels and TUNEL staining of necrotic cells. Hepatic neutrophil infiltration also increased in alcohol-fed mice after IR surgery. However, deletion of

This article presents a retrospective case series of implant site development using titanium mesh (Ti-mesh) in the maxilla. A total of 58 mesh procedures in combination with several different bone grafts (allograft, cellular allograft, and bovine xenograft) and biologics (including recombinant human platelet-derived growth factor, autogenous platelet-rich growth factor, and recombinant human bone morphogenetic protein-2) were performed in 48 patients. Ti-mesh guided bone regeneration procedures were performed 2 to 3 months after extraction of nonrestorable/hopeless teeth, and the implants were placed 6 to 8 months postaugmentation. The mean initial ridge width was 2.0 ± 1.0 mm, and the mean horizontal gain after Ti-mesh procedures was 4.7 ± 1.6 mm. The ridge width was first measured on the cross-sectional presurgical CBCT image and then confirmed clinically during surgical procedures. No statistical difference in the horizontal gain was found among different combinations of bone grafts and biomaterials. Ti-mesh exposure occurred 22% of the time. The middle-aged adults (odds ratio [OR] = 8.59; P = .046) and older adults (OR = 16.66; P = .02) had significantly higher chances of mesh exposure compared to young adults. While all implants were successfully placed, about 56% of the implants had2 mm of bone to the facial aspect of the osteotomy and received additional contour augmentation when placed in a prosthetically appropriate position for a screw-retained restoration. This study demonstrates that although Ti-mesh procedures result in significant bone regeneration in narrow alveolar ridges to predictably allow implant placement, the age-related mesh exposure rate and frequency of need for additional contour grafting should be discussed with patients.

Supplementary Materials from A Multicellular Basis for the Origination of Blast Crisis in Chronic Myeloid Leukemia

Sokal Data from A Multicellular Basis for the Origination of Blast Crisis in Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is characterized by a specific chromosome translocation, and its pathobiology is considered comparatively well understood. Thus, quantitative analysis of CML and its progression to blast crisis may help elucidate general mechanisms of carcinogenesis and cancer progression. Hitherto, it has been widely postulated that CML blast crisis originates mainly via cell-autonomous mechanisms such as secondary mutations or genomic instability. However, recent results suggest that carcinogenic transformation may be an inherently multicellular event, in departure from the classic unicellular paradigm. We investigate this possibility in the case of blast crisis origination in CML. A quantitative, mechanistic cell population dynamics model was employed. This model used recent data on imatinib-treated CML; it also used earlier clinical data, not previously incorporated into current mathematical CML/imatinib models. With the pre-imatinib data, which include results on many more blast crises, we obtained evidence that the driving mechanism for blast crisis origination is a cooperation between specific cell types. Assuming leukemic–normal interactions resulted in a statistically significant improvement over assuming either cell-autonomous mechanisms or interactions between leukemic cells. This conclusion was robust with regard to changes in the model's adjustable parameters. Application of the results to patients treated with imatinib suggests that imatinib may act not only on malignant blast precursors, but also, to a limited degree, on the malignant blasts themselves. Cancer Res; 71(8); 2838–47. ©2011 AACR.

Background:HAR1 is a 118-bp segment that lies in a pair of novel non-coding RNA genes. It shows a dramatic accelerated change with an estimated 18 substitutions in the human lineage since the human–chimpanzee ancestor, compared with the expected 0.27 substitutions based on the slow rate of change in this region in other amniotes. Mutations of HAR1 lead to a different HAR1 secondary structure in humans compared to that in chimpanzees.Methods: We cloned HAR1 into the EF-1α promoter vector to generate transgenic mice. Morris water maze tests and step-down passive avoidance tests were conducted to observe the changes in memory and cognitive abilities of mice. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) between the experimental and control groups. Systematic bioinformatics analysis was used to confirm the pathways and functions that the DEGs were involved in.Results: Memory and cognitive abilities of the transgenic mice were significantly improved. The results of Gene Ontology (GO) analysis showed that Neuron differentiation, Dentate gyrus development, Nervous system development, Cerebral cortex neuron differentiation, Cerebral cortex development, Cerebral cortex development and Neurogenesis are all significant GO terms related to brain development. The DEGs enriched in these terms included Lhx2, Emx2, Foxg1, Nr2e1 and Emx1. All these genes play an important role in regulating the functioning of Cajal–Retzius cells (CRs). The DEGs were also enriched in glutamatergic synapses, synapses, memory, and the positive regulation of long-term synaptic potentiation. In addition, “cellular response to calcium ions” exhibited the second highest rich factor in the GO analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs showed that the neuroactive ligand–receptor interaction pathway was the most significantly enriched pathway, and DEGs also notably enriched in neuroactive ligand–receptor interaction, axon guidance, and cholinergic synapses.Conclusion:HAR1 overexpression led to improvements in memory and cognitive abilities of the transgenic mice. The possible mechanism for this was that the long non-coding RNA (lncRNA) HAR1A affected brain development by regulating the function of CRs. Moreover, HAR1A may be involved in ligand–receptor interaction, axon guidance, and synapse formation, all of which are important in brain development and evolution. Furthermore, cellular response to calcium may play an important role in those processes.

Background:Functional groups, especially herbivorous fishes, are important for mediating benthic community structure on coral reefs. Herbivorous and detritivorous fish display complex feeding behaviour, and research into schooling feeding behaviour and feeding rates, and how these change with environmental and social behavioural variables is lacking. Such knowledge is imperative to infer how herbivory/detritivory will change, in light of changing resources and communities, specifically whether reefs can recover from disturbance. Differences in abundance, feeding rate, body length, diet preferences, and schooling size of three major functional groups, scrapers, grazers and browsers were examined across reef habitats under different fishing regulations, such as no-take restricted zones and open-fishing general use zones. Although marine protected areas have been implemented to conserve reef fish species; further precise management based on ecological behaviour of functional groups is necessary.Results:Scrapers and grazers which were mostly parrotfishes and surgeonfishes were more abundant on reef flats and also displayed the highest feeding rates on reef flats. Although scrapers mainly resided inside the restricted zone, more grazers were found in the general use zone where macroalgae abundance was highest, indicating a higher availability of nutritional resources. Browsers, mostly rabbitfishes, were seldom observed and patchily gathered on the reef flat and slope in both zones. Thus, fishing protection did not appear to benefit grazers and browsers, whereas scrapers gathered on shallow reef flats in the protection zone. Lastly, scraper and grazer feeding rates increased from an individual to paired feeding, and increased with body size, these factors led to variations in feeding behaviours on different habitats under different protection regulations.Conclusions:Fishing protection benefits scrapers which subsequently appears to be resulting in a reduction in algal coverage, and variation in feeding rates was largely related to school sizes. The density of these functionally important grazers was influenced more by changes to benthic composition than protection status. The opposite feeding behaviours of two herbivorous/detritivorous functional groups indicates not only protection status, but fishing gear and size limit regulations are needed to help maintain fisheries and diversity on coral reefs in Taiwan.

The decline of coral reefs has fueled interest in determining whether mesophotic reefs can shield against disturbances and help replenish deteriorated shallower reefs. In this study, we characterized spatial (horizontal and vertical) and seasonal patterns of diversity in coral recruits from Dabaisha and Guiwan reefs at Ludao, Taiwan. Concrete blocks supporting terra‐cotta tiles were placed at shallow (15m) and mesophotic (40m) depths, during 2016–2018. Half of the tiles were retrieved and replaced biannually over three 6‐month surveys (short‐term); the remainder retrieved at the end of the 18‐month (long‐term) survey. 451 recruits were located using fluorescent censusing and identified by DNA barcoding. Barcoding the mitochondrial cytochrome oxidase I (COI) gene resulted in 17 molecular operational taxonomic units (MOTUs). To obtain taxonomic resolution to the generic level, Pocillopora were phylotyped using the mitochondrial open reading frame (ORF), resolving eight MOTUs. Acropora, Isopora, and Montipora recruits were identified by the nuclear PaxC intron, yielding ten MOTUs. Overall, 35 MOTUs were generated and were comprised primarily of Pocillopora and, in fewer numbers, Acropora, Isopora, Pavona, Montipora, Stylophora, among others. 40% of MOTUs recruited solely within mesophotic reefs while 20% were shared by both depth zones. MOTUs recruiting across a broad depth distribution appear consistent with the hypothesis of mesophotic reefs acting as a refuge for shallow‐water coral reefs. In contrast, Acropora and Isopora MOTUs were structured across depth zones representing an exception to this hypothesis. This research provides an imperative assessment of coral recruitment in understudied mesophotic reefs and imparts insight into the refuge hypothesis., We characterized spatial (horizontal and vertical) and seasonal patterns of diversity in coral recruits at shallow and mesophotic reefs in Ludao, Taiwan, using DNA barcoding of the COI, PAXC, and ORF regions. Thirty‐five MOTUs were generated and were comprised primarily of Pocillopora and, in fewer numbers, Acropora, Isopora, Pavona, Montipora, Stylophora, among others. MOTUs recruiting across a broad depth distribution appear consistent with the hypothesis of mesophotic reefs acting as a refuge for shallow‐water coral reefs.

VMP1 is an ER membrane protein with phospholipid scramblase activity that has a critical role in regulating phagophore expansion and autophagosome closure. VMP1 also regulates lipid droplet formation and lipoprotein secretion in cultured cells and zebrafish. In a recent study, we showed that mice with hepatic deletion of Vmp1 have impaired very-low-density lipoprotein (VLDL) secretion and develop nonalcoholic steatohepatitis (NASH) even when fed with regular chow diet. Mechanistically, deletion of Vmp1 leads to decreased hepatic phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels as well as altered PC and PE acyl chain compositions resulting in the accumulation of neutral lipid structures in the ER phospholipid bilayer and decreased pre-VLDL assembly. These studies provide novel mechanistic insights into the non-autophagic functions of VMP1 in regulating lipoprotein secretion.

The Point Intercept Transect (PIT) method has commonly been used in recent decades for estimating the status of coral reef benthic communities. It is a simple method that is efficiently performed underwater, as benthic components are recorded only as presence or absence at specific interval points along transects. Therefore, PIT is also popular in citizen science activities such as Reef Check programs. Longer intervals are commonly associated with longer transects, yet sampling interval length can significantly influence benthic coverage calculations. Despite this, the relative accuracy of longer or shorter intervals related to transect length has not been tested for PIT. In this study, we tested the optimum intervals of PIT for several commonly used transect lengths using the bootstrap method on empirical data collected on tropical coral reefs and non-reefal coral communities. Our results recommend fine intervals of 10 cm or shorter, depending on the length of the transect, to increase the accuracy of estimating benthic community status on coral reefs. Permanent transects should also be considered in long-term monitoring programs to improve data quality.

Background Despite recent rapid progress in method development and biological understanding of induced pluripotent stem (iPS) cells, there has been a relative shortage of tools that monitor the early reprogramming process into human iPS cells. Methods We screened the in-house built fluorescent library compounds that specifically bind human iPS cells. After tertiary screening, the selected probe was analyzed for its ability to detect reprogramming cells in the time-dependent manner using high-content imaging analysis. The probe was compared with conventional dyes in different reprogramming methods, cell types, and cell culture conditions. Cell sorting was performed with the fluorescent probe to analyze the early reprogramming cells for their pluripotent characteristics and genome-wide gene expression signatures by RNA-seq. Finally, the candidate reprogramming factor identified was investigated for its ability to modulate reprogramming efficiency. Results We identified a novel BODIPY-derived fluorescent probe, BDL-E5, which detects live human iPS cells at the early reprogramming stage. BDL-E5 can recognize authentic reprogramming cells around 7 days before iPS colonies are formed and stained positive with conventional pluripotent markers. Cell sorting of reprogrammed cells with BDL-E5 allowed generation of an increased number and higher quality of iPS cells. RNA sequencing analysis of BDL-E5-positive versus negative cells revealed early reprogramming patterns of gene expression, which notably included CREB1. Reprogramming efficiency was significantly increased by overexpression of CREB1 and decreased by knockdown of CREB1. Conclusion Collectively, BDL-E5 offers a valuable tool for delineating the early reprogramming pathway and clinically applicable commercial production of human iPS cells.

Ocean warming is increasing the incidence, scale, and severity of global-scale coral bleaching and mortality, culminating in the third global coral bleaching event that occurred during record marine heatwaves of 2014-2017. While local effects of these events have been widely reported, the global implications remain unknown. Analysis of 15,066 reef surveys during 2014-2017 revealed that 80% of surveyed reefs experienced significant coral bleaching and 35% experienced significant coral mortality. The global extent of significant coral bleaching and mortality was assessed by extrapolating results from reef surveys using comprehensive remote-sensing data of regional heat stress. This model predicted that 51% of the world’s coral reefs suffered significant bleaching and 15% significant mortality, surpassing damage from any prior global bleaching event. These observations demonstrate that global warming’s widespread damage to coral reefs is accelerating and underscores the threat anthropogenic climate change poses for the irreversible transformation of these essential ecosystems.

We report outcomes 7 years following implementation of a pediatric oncofertility team. We compare our baseline oncofertility survey to 44 post-intervention survey respondents and electronic medical record documentation for 149 patients treated in 2019. 95% of post-intervention survey respondents recalled fertility counseling (baseline 70%, p=0.004) and 89.3% were appropriately referred for fertility preservation (baseline 50%, p=0.017). Counseling was documented in 60.4% of charts; 81% of patients were appropriately referred for fertility preservation. Fertility preservation outcomes differed by sex. Creation of an oncofertility team produced sustained improvements in fertility counseling and fertility preservation referral.

Polycyathus chaishanensis is a symbiotic caryophyllid coral described from a single population in a tidal pool off Chaishan, Kaohsiung, Taiwan. Due to its rarity, P. chaishanensis was declared a critically-endangered species under the Taiwan Wildlife Protection Act. In May 2017, a P. chaishanensis colony was discovered in the intertidal area of the Datan Algal Reef, Taoyuan, Taiwan. To determine whether this is a stable population in the algal reef, a demographic census—including data on occurrence, distribution, and colony size—was carried out in the algal reef in southern Taoyuan. Intertidal censuses and sediment collections were conducted at five different sections—Baiyu, Datan G1, Datan G2, Yongxing, and Yongan algal reefs—during the monthly spring low tide from July 2018 to January 2019. In total, 84 colonies—23 in Datan G1 and 61 in Datan G2—were recorded from a tidal range of − 160 to − 250 cm, according to the Taiwan Vertical Datum 2001 compiled by the Central Weather Bureau. No P. chaishanensis was found in Baiyu, Yongxing, or Yongan. The P. chaishanensis colony sizes ranged from 2.55 to 81.5 cm in diameter, with the larger P. chaishanensis present in the lower intertidal zone. Sediment was extremely high, with monthly site averages ranging from 3,818.26 to 29,166.88 mg cm−2 day−1, and there was a significant difference between sites and months, both of which affected the distribution of P. chaishanensis in the algal reef. Our study confirms the existence of a second population of P. chaishanensis in Taiwan, highlighting the importance of the Datan Algal Reef for the survival and protection of this critically-endangered caryophyllid coral and why it is so urgent that the reef should be conserved.

In the past decade, the frequency of mass coral bleaching events has increased due to seawater temperature anomalies persisting for longer periods. Coral survival from temperature anomalies has been based on how each species in each location responds to stress, which is unique to individual species and may be due to the way stressful experiences accumulate through time in the form of ecological and physiological memory. A deeper understanding of ecological and physiological memory in corals is necessary to understand their survival strategies into the future. Laboratory experiments can help us simulate seawater temperatures experienced by corals in the past and compare their responses to those of the present and future. In this study, we sampled corals with different life history traits from one location perturbed by seawater temperature incursions (variable site) and from a second, relatively undisturbed location (stable site). We sampled across two seasons to observe the responses to bleaching threshold temperatures in the past (1998-29 °C), present (2018-31 °C), and future (2050-33 °C). Corals were healthy at 29 °C and 31 °C, but a fast-growing, temperature-susceptible coral species experienced high mortality at 33 °C compared to a slow-growing, temperature-resistant coral species. Moreover, corals from the variable site and during the spring season fared better under temperature stress. The results of this study provide insight into the possible role of life-history traits on coral's response to seasons and locations in terms of memory to long-term and short-term thermal anomalies and climate change.

Understanding the potential inhalation toxicity of poorly characterized aerosols is challenging both because aerosols may contain numerous chemicals and because it is difficult to predict which chemicals may present significant inhalation toxicity concerns at the observed levels. We have developed a novel systematic procedure to address these challenges through non-targeted chemical analysis by two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOFMS) and assessment of the results using publicly available toxicity data to prioritize the tentatively identified detected chemicals according to potential inhalation toxicity. The procedure involves non-targeted chemical analysis of aerosol samples utilizing GC × GC-TOFMS, which is selected because it is an effective technique for detecting chemicals in complex samples and assigning tentative identities according to the mass spectra. For data evaluation, existing toxicity data (e.g. from the U.S. Environmental Protection Agency CompTox Chemicals Dashboard) are used to calculate multiple toxicity metrics that can be compared among the tentatively identified chemicals. These metrics include hazard quotient, incremental lifetime cancer risk, and metrics analogous to hazard quotient that we designated as exposure–(toxicology endpoint) ratios. We demonstrated the utility of our procedure by detecting, identifying, and prioritizing specific chemicals of potential inhalation toxicity concern in the mainstream smoke generated from the machine-smoking of marijuana blunts. By designing a systematic approach for detecting and identifying numerous chemicals in complex aerosol samples and prioritizing the chemicals in relation to different inhalation toxicology endpoints, we have developed an effective approach to elucidate the potential inhalation toxicity of aerosols.

Purpose: We report findings from the first-in-human study of [ 11 C]MDTC, a radiotracer developed to image the cannabinoid receptor type 2 (CB2R) with positron emission tomography (PET). Methods: Ten healthy adults were imaged according to a 90 min dynamic PET protocol after bolus intravenous injection of [ 11 C]MDTC. Five participants also completed a second [ 11 C]MDTC PET scan to assess test-retest reproducibility of receptor-binding outcomes. The kinetic behavior of [ 11 C]MDTC in human brain was evaluated using a metabolite-corrected arterial plasma input function with compartmental modeling and graphical analysis approaches. Four additional healthy adults completed whole-body [ 11 C]MDTC PET/CT to calculate organ doses and the whole-body effective dose. Results: [ 11 C]MDTC brain PET and [ 11 C]MDTC whole body PET/CT was well-tolerated. The model of choice for fitting the time activity curves (TACs) across brain regions of interest was a two-tissue compartment model with the blood volume fraction included as a fitting parameter (2TCM-vB). Regional distribution volume (V T ) values computed from Logan graphical analysis correlated well with those estimated using the 2TCM-vB model. Cortical regions and thalamus had higher V T than brainstem, striatum, hippocampus, and corpus callosum. Test-retest reliability of V T demonstrated a mean absolute variability of 7.13%, with an intraclass correlation coefficient 0.91. The measured effective dose of [ 11 C]MDTC was 5.29 µSv/MBq. Conclusion: These data support use of [ 11 C]MDTC PET for in vivo neuroimaging of CB2R in humans. Future in vivo studies using [ 11 C]MDTC PET in neuroinflammatory conditions are needed to assess the detection of high expression of the CB2R by activated microglia in human brain.

Background: LncRNA HAR1A, which is explicitly expressed in Cajal-Retzius neurons (CRs), has been reported to be related to the development of the human brain. As one of the human accelerated regions (HARs) gene, it plays an important role in central neural evolution. Dysregulation of lncRNA HAR1A was associated with many central nervous system diseases. Methods:We cloned human gene HAR1A into the EF-1α promoter vector to make the transgenic mice. To observe the changes in memory and cognitive ability of mice, we conducted the Morris water maze (MWM) test and step-down passive avoidance test. RNA-seq analysis was performed to identify the differentially expressed genes (DEGs) of the experiment and control group. Systematic bioinformatic analysis was used to confirm the pathway and function that the DEGs enriched in. 523 human gene expression datasets were downloaded from The Cancer Genome Atlas (TCGA) for Co-expression analysis. Through Co-expression analysis, we obtained the Protein-Protein Interactions Network (PPI-Net) and enrichment pathways of LncRNA HAR1A's co-expression genes in human. Results:The memory and cognitive ability of the transgene mice were significantly improved. Results of GO analysis showed that cerebral cortex development is the most significant function related to HAR1A in brain development. DEGs enriched in this function included Lhx2, Emx2, Foxg1, Nr2e1, Emx1. They all play an important role in the regulation of CRs' function. "Cellular response to calcium ion" exhibited the highest rich factor in the Gene Ontology (GO) analysis. Core genes in the PPI-Net were SNAP25, GRIN1, SYN1, DLG4, CAMK2A. SNAP25, SYN1 relate to synaptic function. GRIN1, DLG4 and CAMK2A relate to synapse formation. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs and HAR1A 's Co-expressed genes in 523 human gene expression datasets show that synapse, axon guidance, synaptic signaling and ligand-receptor interaction are significant.Conclusions:Overexpress HAR1A will improve the memory and cognitive ability of the transgene mice. The possible mechanism is HAR1A affects brain development by regulating CRs' function. Moreover, HAR1A may be involved in ligand-receptor interaction, Axon guidance and synapse formation, which are important for brain development and evolution. Cellular response to calcium may play an important role in those process.

The east Taiwan Strait is largely fringed by sandy and muddy habitats. However, a massive algal reef made of crustose coralline algae has been found along the coast off Taoyuan city in northwestern Taiwan. The porous structure of Taoyuan Algal Reef harbors high abundance and diversity in marine organisms, including the ferocious reef crab, Eriphia ferox. Such a pivotal geographic location and unique ecological features make Taoyuan Algal Reef a potential stepping stone connecting biotic reefs in the east Taiwan Strait, South China Sea to the south, and even the high latitude of Japan to the north. In this study, we examined the population connectivity and historical demography of E. ferox by analyzing mitochondrial cytochrome oxidase I (COI) fragments of 317 individuals sampled from 21 localities in the northwestern Pacific. Our analyses of haplotype network and pairwise FST comparisons revealed a lack of phylogeographical structure among E. ferox populations, implying the existence of a migration corridor connecting the South and East China Seas through the east Taiwan Strait. Multiple lines of evidence, including significant values in neutrality tests, unimodally shaped mismatch distributions, and Bayesian skyline plots elucidated the rapid population growth of E. ferox following the sea-level rise after Last Glacial Maximum (ca. 2–10 Ka). Such demographic expansion in E. ferox coincided with the time when Taoyuan Algal Reef started to build up around 7,500 years ago. Coalescent migration analyses further indicated that the large and continuous E. ferox population exclusively found in Datan Algal Reef, the heart of Taoyuan Algal Reef, was a source population exporting migrants both northward and southward to the adjacent populations. The bidirectional gene flow should be attributed to larval dispersal by ocean currents and secondary contact due to historical population expansion. Instead of serving as a stepping stone, our results support that Taoyuan Algal Reef is an essential population source for biotic reef-associated species along the east Taiwan Strait, and highlight the importance of conserving such a unique ecosystem currently threatened by anthropogenic development.

Global warming threatens reef-building corals with large-scale bleaching events; therefore, it is important to discover potential adaptive capabilities for increasing their temperature resistance before it is too late. This study presents two coral species (Platygyra verweyi and Isopora palifera) surviving on a reef having regular hot water influxes via a nearby nuclear power plant that exhibited completely different bleaching susceptibilities to thermal stress, even though both species shared several so-called “winner” characteristics (e.g., containing Durusdinium trenchii, thick tissue, etc.). During acute heating treatment, algal density did not decline in P. verweyi corals within three days of being directly transferred from 25 to 31 °C; however, the same treatment caused I. palifera to lose P. verweyi over I. palifera. Moreover, P. verweyi also contained significantly higher saturated and lower mono-unsaturated fatty acids, especially a long-chain saturated fatty acid (C22:0), than I. palifera, and was consistently associated with the symbiotic bacteria Endozoicomonas, which was not found in I. palifera. However, antibiotic treatment and inoculation tests did not support Endozoicomonas having a direct contribution to thermal resistance. This study highlights that, besides its association with a thermally tolerable algal symbiont, a high level of constitutive antioxidant enzymes in the coral host is crucial for coral survivorship in the more fluctuating and higher temperature environments.

Atrial septal defects (ASDs) are the most common types of cardiac septal defects in congenital heart defects. In addition to traditional therapy, interventional closure has become the main treatment method. However, the molecular events and mechanisms underlying the repair progress by occlusion device remain unknown. In this study, we aimed to characterize differentially expressed genes (DEGs) in the blood of patients treated with occlusion devices (metal or poly-L-lactic acid devices) using RNA-sequencing, and further validated them by qRT-PCR analysis to finally determine the expression of key mediating genes after closure of ASD treatment. The result showed that total 1,045 genes and 1,523 genes were expressed differently with significance in metal and poly-L-lactic acid devices treatment, respectively. The 115 overlap genes from the different sub-analyses are illustrated. The similarities and differences in gene expression reflect that the body response process involved after interventional therapy for ASDs has both different parts that do not overlap and the same part that crosses. The same portion of body response regulatory genes are key regulatory genes expressed in the blood of patients with ASDs treated with closure devices. The gene ontology enrichment analysis showed that biological processes affected in metal device therapy are immune response with CXCR4 genes and poly-L-lactic acid device treatment, and the key pathways are nuclear-transcribed mRNA catabolic process and proteins targeting endoplasmic reticulum process with ribosomal proteins (such as RPS26). We confirmed that CXCR4, TOB1, and DDIT4 gene expression are significantly downregulated toward the pre-therapy level after the post-treatment in both therapy groups by qRT-PCR. Our study suggests that the potential role of CXCR4, DDIT4, and TOB1 may be key regulatory genes in the process of endothelialization in the repair progress of ASDs, providing molecular insights into this progress for future studies.

Taiwan’s shallow coral reef habitats (0–30 m) and their scleractinian fauna are well-studied but its mesophotic zone (30–90 m) remains underexamined. This study documents mesophotic (38–60 m) habitat and species diversity at Ludao, Taiwan. In northern and southern Ludao, mesophotic habitats display low-grade slopes (

Structural complexity is an important feature to understand reef resilience abilities, through its role in mediating predator-prey interactions, regulating competition, and promoting recruitment. Most of the current methods used to measure reef structural complexity fail to quantify the contributions of fine and coarse scales of rugosity simultaneously, while other methods require heavy data computation. In this study, we propose estimating reef structural complexity based on high-resolution depth profiles to quantify the contributions of both fine and coarse rugosities. We adapted the root mean square of the deviation from the assessed surface profile (Rq) with polynomials. The efficiency of the proposed method was tested on nine theoretical cases and 50 in situ transects from South Taiwan, and compared to both the chain method and the visual rugosity index commonly employed to characterize reef structural complexity. The Rq indices proposed as rugosity estimators in this study consider multiple levels of reef rugosity, which the chain method and the visual rugosity index fail to apprehend. Furthermore, relationships were found between Rq scores and specific functional groups in the benthic community. Indeed, the fine scale rugosity of the South Taiwan reefs mainly comes from biotic components such as hard corals, while their coarse scale rugosity is essentially provided by the topographic variations that reflect the geological context of the reefs. This approach allows identifying the component of the rugosity that could be managed and which could, ultimately, improve strategies designed for conservation.

Global warming threatens reef-building corals with large-scale bleaching events; therefore, it is important to discover potential adaptive capabilities for increasing their temperature resistance before it is too late. This study presents two coral species (Platygyra verweyi and Isopora palifera) surviving on a reef having regular hot water influxes via a nearby nuclear power plant that exhibited completely different bleaching susceptibilities to thermal stress, even though both species shared several so-called “winner” characteristics (e.g., containing Durusdinium trenchii, thick tissue, etc.). During acute heating treatment, algal density did not decline in P. verweyi corals within three days of being directly transferred from 25 to 31 °C; however, the same treatment caused I. palifera to lose

Over the past few decades, extreme events—such as ocean warming, typhoons, and coral bleaching—have been increasing in intensity and frequency, threatening coral reefs from the physiological to ecosystem level. In the present study, the impacts of rising seawater temperatures, typhoons, and coral bleaching events on benthic communities were seasonally assessed over a 21 month-period, using photo-transects at 11 sites in Kenting National Park (KNP), Taiwan. Between August 2015 and April 2017, seven typhoon events were recorded and in situ seawater temperatures in KNP reached a maximum of 31.2 °C, as opposed to an average maximum SST of 28.8 °C (2007–2016). The state and response of benthic communities to these events were interpreted based on the environmental conditions of KNP. The repeated storms lowered the levels of thermal stress during the 2015–2016 El Niño event and may have mitigated its impact on the Taiwanese coral reefs. However, storm-induced local shifts from coral to macro-algae dominance were observed. Storms may mitigate the negative effects of heatwaves, but the mechanical damage induced by the storms may also decrease the structural complexity of reefs and their associated diversity. Eventually, despite reef persistence, the composition and function of remnant communities may profoundly diverge from those in regions with less active storms.

The crustose calcareous alga, Ramicrusta textilis Pueschel and G.W. Saunders (Peyssonneliaceae, Rhodophyta), was recently observed to overgrow dead and living corals in shallow lagoon patch reefs of Dongsha Atoll, South China Sea. DNA barcoding revealed that R. textilis frequently co-occurred in a complex with other crustose algae of the family Peyssonneliaceae and the genus Lobophora, forming patchy crusts that cover 3%–29% of the benthic substrate. This is the first record R. textilis overgrowing corals in the Pacific Ocean.

Acute limb ischemia (ALI) represents one of the most common emergent scenarios encountered by a vascular specialist. Despite expedient revascularization, high rates of limb loss are reported along with high mortality rates which are second only to ruptured abdominal aortic aneurysms. Surgical revascularization is standard of care. Endovascular techniques as an alternative have emerged to be appropriate first line therapy when addressing the threatened limb. We review the etiology and classification of ALI and current endovascular techniques and evidence to date in the management of patients acutely presenting with extremity ischemia.

The first occurrence of the cyanobacteriosponge

Terpios hoshinota is an aggressive, space-competing sponge that kills various stony corals. Outbreaks of this species have led to intense damage to coral reefs in many locations. Here, the first large-scale 16S rRNA gene survey across three oceans revealed that bacteria related to the taxa Prochloron, Endozoicomonas, SAR116, Ruegeria, and unclassified Proteobacteria were prevalent in T. hoshinota. A Prochloron-related bacterium was the most dominant and prevalent cyanobacterium in T. hoshinota. The complete genome of this uncultivated cyanobacterium and pigment analysis demonstrated that it has phycobiliproteins and lacks chlorophyll b, which is inconsistent with the definition of Prochloron. Furthermore, the cyanobacterium was phylogenetically distinct from Prochloron, strongly suggesting that it should be a sister taxon to Prochloron. Therefore, we proposed this symbiotic cyanobacterium as a novel species under the new genus Candidatus Paraprochloron terpiosi. Comparative genomic analyses revealed that 'Paraprochloron' and Prochloron exhibit distinct genomic features and DNA replication machinery. We also characterized the metabolic potentials of 'Paraprochloron terpiosi' in carbon and nitrogen cycling and propose a model for interactions between it and T. hoshinota. This study builds a foundation for the study of the T. hoshinota microbiome and paves the way for better understanding of ecosystems involving this coral-killing sponge.

The integrity of coral reefs has increasingly been threatened by human development and climate change. As a result, the concept of ecological resilience – an ecosystem’s capability to resist and recover from environmental stressors – has become an important aspect of coral reef conservation. In this study, coral reef resilience was quantitatively scored in Kenting National Park (KNP), Taiwan, using four different assessment frameworks: the first uses the opinions of local reef experts, the second includes metrics specific to the local reef context, the third combines the previous two approaches, and the fourth relies solely on ecological metrics from biodiversity surveys. To evaluate the accuracy of each assessment, the resulting resilience scores were compared with historical coral recovery rates, which served as a proxy for resilience. While each approach to measuring resilience has its merits and drawbacks, the picture of resilience became clearest when a few key indicators were included to reflect core ecosystem processes. Trends in resilience scores varied depending on the makeup of the assessment's indicators, and there was little correlation between the baseline metrics measured using different data collection methods. However, all resilience assessment trends indicated that KNP’s Nanwan area is high in resilience. This is likely due to the effects of local tidally-induced upwelling, which significantly relieve the growing thermal stress placed on surrounding coral communities. Ultimately, the most successful assessments were those that empirically quantified ecological processes and local factors with only a few indicators, rather than broader approaches that measured many indicators. These findings are particularly relevant for reef managers to consider as they develop and employ resilience-based management strategies.