bluuebunny/crossref_metadata_2025 huggingface dataset:
Swimming performance of subarctic Calanus spp. facing downward currents
Authors: Weidberg N , DiBacco C , Pezzola C , Rebiffe E , Basedow SL
Published: February 2021

Calanoid copepods dominate mesozooplankton communities in temperate and Nordic seas. The ability of copepods to remain and feed in productive surface waters depends on their ability to overcome downward flows. In this study, we assessed the swimming performance of subarctic Calanus spp. and tested how the copepods can retain their vertical position in a representative range of downward currents (between 0 and 5.4 cm s-1) simulated in a downwelling flume. Mean vertical and horizontal copepod swimming velocities and accelerations, movement periodicity and trajectory complexity were obtained by tracking individual trajectories in the field of view of 2 cameras. Copepod swimming velocity increased with increasing downward flow and matched downward flows up to 2 cm s-1. Beyond 2 cm s-1, animals were still able to significantly reduce their sinking rates, but their motions changed. Trajectories became simpler, swimming velocities changed on shorter time scales and instantaneous acceleration increased. These results are consistent with predictions of balancing depth retention against encounter rates with food and predators. Frequency distributions of vertical swimming speeds were mostly unimodal, with entire experimental populations responding in the same way. Coordination of movements and the ability to resist moderate downwelling flows can result in the accumulation of copepods in large surface swarms as observed in the field.
Protective role of resilience on COVID-19 impact on the quality of life of nursing students in the Philippines
Authors: Guillasper Jean Nunez , Oducado Ryan Michael Flores , Soriano Gil Platon
Published: February 2021

Background: Studies have shown that resilience has a buffering effect on mental health problems. However, the influence of resilience on the impact on the Quality of Life (QoL) in the context of the COVID-19 pandemic has not been well documented.
Objective: This study examined the influence of resilience on the COVID-19 impact on QoL among nursing students.
Methods: A cross-sectional research design was utilized. Three hundred and forty-five students of a government-funded nursing school in the Philippines responded in the web-based survey. Data were gathered using two adopted instruments from 18 to 31 August 2020. Test for differences and correlational analyses were performed.
Results: The COVID-19 pandemic had a moderate impact on the QoL of nursing students. The COVID-19 impact on QoL significantly varied with sex and the nearby presence of COVID-19 cases. Bivariate analysis revealed a significant moderate inverse relationship between psychological resilience and the impact of COVID-19 on QoL.
Conclusion: Resilience has a protective influence on the impact on QoL concerning main areas of mental health in the context of the COVID-19 pandemic. Understanding the factors and developing interventions that build the resilience of students is a focal point of action for nursing schools.
Effects of endurance exercise training on markers of cholesterol absorption and synthesis
Authors: Wilund KR , Feeney LA , Tomayko EJ , Weiss EP , Hagberg JM
Published: February 2021

Abnormal cholesterol metabolism, including low intestinal
cholesterol absorption and elevated synthesis, is prevalent in
diabetes, obesity, hyperlipidemia, and the metabolic syndrome.
Diet-induced weight loss improves cholesterol absorption in these
populations, but it is not known if endurance exercise training
also improves cholesterol homeostasis. To examine this, we
measured circulating levels of campesterol, sitosterol, and
lathosterol in 65 sedentary subjects (average age 59 years; with
at least one metabolic syndrome risk factor) before and after
6 months of endurance exercise training. Campesterol and
sitosterol are plant sterols that correlate with intestinal
cholesterol absorption, while lathosterol is a marker of whole
body cholesterol synthesis. Following the intervention, plant
sterol levels were increased by 10 % (p<0.05), but there was no
change in plasma lathosterol. In addition, total and LDLcholesterol were reduced by 0.16 mmol and 0.10 mmol,
respectively (p<0.05), while HDL-C levels increased by
0.09 mmol (p<0.05). Furthermore, the change in plant sterols
was positively correlated with the change in VO2max (r = 0.310,
p=0.004), independent of other metabolic syndrome risk factors.
These data indicate that exercise training reduces plasma
cholesterol despite increasing cholesterol absorption in subjects
with metabolic syndrome risk factors.
Endothelial dysfunction in insulin-resistant rats is associated with oxidative stress and COX pathway dysregulation
Authors: Oudot A , Behr-Roussel D , Compagnie S , Caisey S , Le Coz O , Gorny D , Alexandre L , Giuliano F
Published: February 2021

Because insulin resistance is inevitably associated with
cardiovascular complications, there is a need to further
investigate the potential involvement of oxidative stress and the
cyclo-oxygenase (COX) pathway in the vascular modifications
associated to this pathological context. Endothelial function was
evaluated in control and fructose-fed rats (FFR) by i) in vitro
study of endothelium-dependent and -independent relaxations of
aortic rings, and ii) in vivo telemetric evaluation of pressor
response to norepinephrine. After 9 weeks of diet, FFR displayed
hypertriglyceridemia, hyperinsulinemia and exaggerated response
to glucose overload. Aortic rings from control rats and FFR
exhibited comparable endothelium-dependent relaxations to Ach.
In the presence of indomethacin, relaxations were significantly
reduced. FFR showed exaggerated pressor responses to
norepinephrine that were abolished with indomethacin. Urinary
nitrites/nitrates, 8-isoprostanes and thromboxane B2 excretion
levels were markedly enhanced in FFR, whereas the plasma
levels of 6-keto prostaglandin F1α were unchanged. In conclusion,
fructose overload in rats induced hypertriglyceridemia and insulin
resistance associated with an enhanced oxidative stress. This was
associated with COX pathway dysregulation which could be one
of the contributors to subsequent vascular dysfunction.
Consequently, reduction of oxidative stress and regulation of the
COX pathway could represent new potential therapeutic
strategies to limit vascular dysfunction and subsequent
cardiovascular complications associated with insulin resistance.
Resting membrane potential and Na+,K+-ATPase of rat fast and slow muscles during modeling of hypogravity
Authors: Tyapkina O , Volkov E , Nurullin L , Shenkman B , Kozlovskaya I , Nikolsky E , Vyskočil F
Published: February 2021

Antiorthostatic hindlimb suspension (unloading) decreased the
resting membrane potential (RMP) of skeletal muscle fibers in
fast extensor digitorum longus (EDL) and slow soleus (SOL)
muscle of the rat by about 10 % within 7 days and more.
Inactivation of the membrane Na+, K+-pump by ouabain brought
about similar depolarization as unloading. The increased sodium
permeability of the membrane was excluded as the major cause
of this depolarization by experiments in which TRIS was
substituted for Na+ in the medium. On the other hand, the
decrease in the electrogenic participation of the Na+,K+-pump is
apparently one of the causes of RMP decrease during
hypogravity, in EDL muscle in particular.
Retreating to the Country: R.C. Sherriff's Rural Interwar Novels & Environmental Politics
Authors: Sultzbach Kelly
Published: February 2021

This essay contextualizes two of R.C. Sherriff's inter-war novels, Greengates (1936) and The Hopkins Manuscript (1939), within modernist debates about countryside preservation as well as noting their ongoing relevance to contemporary environmental politics. By creating characters who are both sympathetic war veterans and easily satirized figures of patriarchy and privilege, Sherriff engages complex themes of capitalist consumerism, ‘us’ and ‘them’ attitudes about land policy, and fraught impulses of pastoral nostalgia. These novels resist facile diatribe; instead, they force the reader to inhabit the emotional swings inherent in the lived experience of love and sacrifice required for environmental preservation.
The Nose as a Route for Therapy: Part 1. Pharmacotherapy
Authors: Cingi Cemal , Bayar Muluk Nuray , Mitsias Dimitrios I. , Papadopoulos Nikolaos G. , Klimek Ludger , Laulajainen-Hongisto Anu , Hytönen Maija , Toppila-Salmi Sanna Katriina , Scadding Glenis Kathleen
Published: February 2021

This article reviews nasal structure and function in the light of intranasal pharmacotherapy. The nose provides an accessible, fast route for local treatment of nose and sinus diseases, with lower doses than are necessary systemically and few adverse effects. It can also be used for other medications as it has sufficient surface area protected from local damage by mucociliary clearance, absence of digestive enzymes, responsive blood flow, and provides a rapid route to the central nervous system.
CTCF Mediates Replicative Senescence Through POLD1
Authors: Hou Yuli , Song Qiao , Gao Shichao , Zhang Xiaomin , Wang Yaqi , Liu Jing , Fu Jingxuan , Cao Min , Wang Peichang
Published: February 2021

POLD1, the catalytic subunit of DNA polymerase δ, plays a critical role in DNA synthesis and DNA repair processes. Moreover, POLD1 is downregulated in replicative senescence to mediate aging. In any case, the components of age-related downregulation of POLD1 expression have not been fully explained. In this article, we elucidate the mechanism of the regulation of POLD1 at the transcription level and found that the transcription factor CCCTC-binding factor (CTCF) was bound to the POLD1 promoter area in two sites. The binding level of CTCF for the POLD1 promoter appeared to be related to aging and was confirmed to be positively controlled by the CTCF level. Additionally, cell senescence characteristics were detected within the cells transfected with short hairpin RNA (shRNA)-CTCF, pLenti-CMV-CTCF, shRNA-POLD1, and pLenti-CMV-POLD1, and the results showed that the CTCF may contribute to the altered expression of POLD1 in aging. In conclusion, the binding level of CTCF for the POLD1 promoter intervened by an age-related decrease in CTCF and downregulated the POLD1 expression in aging. Moreover, the decrease in CTCF-mediated POLD1 transcription accelerates the progression of cell aging.
Single-Cell RNA Sequencing With Combined Use of Bulk RNA Sequencing to Reveal Cell Heterogeneity and Molecular Changes at Acute Stage of Ischemic Stroke in Mouse Cortex Penumbra Area
Authors: Guo Kang , Luo Jianing , Feng Dayun , Wu Lin , Wang Xin , Xia Li , Tao Kai , Wu Xun , Cui Wenxing , He Yixuan , Wang Bing , Zhao Zhenwei , Zhang Zhiguo
Published: February 2021

Stroke has been the leading cause of adult morbidity and mortality over the past several years. After an ischemic stroke attack, many dormant or reversibly injured brain cells exist in the penumbra area. However, the pathological processes and unique cell information in the penumbra area of an acute ischemic stroke remain elusive. We applied unbiased single cell sequencing in combination with bulk RNA-seq analysis to investigate the heterogeneity of each cell type in the early stages of ischemic stroke and to detect early possible therapeutic targets to help cell survival. We used these analyses to study the mouse brain penumbra during this phase. Our results reveal the impact of ischemic stroke on specific genes and pathways of different cell types and the alterations of cell differentiation trajectories, suggesting potential pathological mechanisms and therapeutic targets. In addition to classical gene markers, single-cell genomics demonstrates unique information on subclusters of several cell types and metabolism changes in an ischemic stroke. These findings suggest that Gadd45b in microglia, Cyr61 in astrocytes, and Sgk3 in oligodendrocytes may play a subcluster-specific role in cell death or survival in the early stages of ischemic stroke. Moreover, RNA-scope multiplex in situ hybridization and immunofluorescence staining were applied to selected target gene markers to validate and confirm the existence of these cell subtypes and molecular changes during acute stage of ischemic stroke.
mtDNA Heteroplasmy at the Core of Aging-Associated Heart Failure. An Integrative View of OXPHOS and Mitochondrial Life Cycle in Cardiac Mitochondrial Physiology
Authors: Elorza Alvaro A. , Soffia Juan Pablo
Published: February 2021

The most common aging-associated diseases are cardiovascular diseases which affect 40% of elderly people. Elderly people are prone to suffer aging-associated diseases which are not only related to health and medical cost but also to labor, household productivity and mortality cost. Aging is becoming a world problem and it is estimated that 21.8% of global population will be older than 65 years old in 2050; and for the first time in human history, there will be more elderly people than children. It is well accepted that the origin of aging-associated cardiovascular diseases is mitochondrial dysfunction. Mitochondria have their own genome (mtDNA) that is circular, double-stranded, and 16,569 bp long in humans. There are between 500 to 6000 mtDNA copies per cell which are tissue-specific. As a by-product of ATP production, reactive oxygen species (ROS) are generated which damage proteins, lipids, and mtDNA. ROS-mutated mtDNA co-existing with wild type mtDNA is called mtDNA heteroplasmy. The progressive increase in mtDNA heteroplasmy causes progressive mitochondrial dysfunction leading to a loss in their bioenergetic capacity, disruption in the balance of mitochondrial fusion and fission events (mitochondrial dynamics, MtDy) and decreased mitophagy. This failure in mitochondrial physiology leads to the accumulation of depolarized and ROS-generating mitochondria. Thus, besides attenuated ATP production, dysfunctional mitochondria interfere with proper cellular metabolism and signaling pathways in cardiac cells, contributing to the development of aging-associated cardiovascular diseases. In this context, there is a growing interest to enhance mitochondrial function by decreasing mtDNA heteroplasmy. Reduction in mtDNA heteroplasmy is associated with increased mitophagy, proper MtDy balance and mitochondrial biogenesis; and those processes can delay the onset or progression of cardiovascular diseases. This has led to the development of mitochondrial therapies based on the application of nutritional, pharmacological and genetic treatments. Those seeking to have a positive impact on mtDNA integrity, mitochondrial biogenesis, dynamics and mitophagy in old and sick hearts. This review covers the current knowledge of mitochondrial physiopathology in aging, how disruption of OXPHOS or mitochondrial life cycle alter mtDNA and cardiac cell function; and novel mitochondrial therapies to protect and rescue our heart from cardiovascular diseases.
Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation
Authors: Liu Lixian , Xing Liying , Chen Rongyuan , Zhang Jianing , Huang Yuye , Huang Lijuan , Xie Bingbing , Ren Xiangrong , Wang Shasha , Kuang Haiqing , Lin Xianchai , Kumar Anil , Kim Jong Kyong , Lee Chunsik , Li Xuri
Published: February 2021

The mitogen-inducible gene 6 (MIG6) is an adaptor protein widely expressed in vascular endothelial cells. However, it remains unknown thus far whether it plays a role in angiogenesis. Here, using comprehensive in vitro and in vivo model systems, we unveil a potent anti-angiogenic effect of MIG6 in retinal development and neovascularization and the underlying molecular and cellular mechanisms. Loss of function assays using genetic deletion of Mig6 or siRNA knockdown increased angiogenesis in vivo and in vitro, while MIG6 overexpression suppressed pathological angiogenesis. Moreover, we identified the cellular target of MIG6 by revealing its direct inhibitory effect on vascular endothelial cells (ECs). Mechanistically, we found that the anti-angiogenic effect of MIG6 is fulfilled by binding to SHC1 and inhibiting its phosphorylation. Indeed, SHC1 knockdown markedly diminished the effect of MIG6 on ECs. Thus, our findings show that MIG6 is a potent endogenous inhibitor of angiogenesis that may have therapeutic value in anti-angiogenic therapy.
Deep Reinforcement Learning Algorithms for Multiple Arc-Welding Robots
Authors: Xu Lei-Xin , Chen Yang-Yang
Published: February 2021

The applications of the deep reinforcement learning method to achieve the arcs welding by multi-robot systems are presented, where the states and the actions of each robot are continuous and obstacles are considered in the welding environment. In order to adapt to the time-varying welding task and local information available to each robot in the welding environment, the so-called multi-agent deep deterministic policy gradient (MADDPG) algorithm is designed with a new set of rewards. Based on the idea of the distributed execution and centralized training, the proposed MADDPG algorithm is distributed. Simulation results demonstrate the effectiveness of the proposed method.
Fluid Inclusions and H–O–C–S–Pb Isotopic Systematics of the Jinba Gold Deposit, NW China: Implications for Ore Genesis
Authors: Li Shun-Da , Chen Chuan , Gao Ling-Ling , Xia Fang , Zhang Xue-Bing , Wang Ke-Yong
Published: February 2021

The Jinba gold deposit is located in the Maerkakuli Shear Zone of the south Altay Orogenic Belt, NW China. Mineralization types are classified as altered rock–and quartz vein–type. Orebodies occur as veins or lenses controlled by NW–trending faults, and are hosted in phyllite (Early–Middle Devonian Ashele Formation) and plagiogranite (Early Devonian Habahe Pluton). Three paragenetic stages were identified: early quartz–pyrite–gold (Stage 1), middle quartz–chalcopyrite (Stage 2), and late calcite–quartz–galena–sphalerite (Stage 3). Fluid inclusions within the deposit are liquid–rich aqueous (LV–type), vapor–rich aqueous (VL–type), carbonic–aqueous (LC–type), and purely carbonic (C–type) FIs. Homogenization temperatures for stages 1–3 FIs were 373–406 °C, 315–345 °C, and 237–265 °C, respectively. Fluid salinities for stages 1–3 were 2.1–13.6 wt%, 3.2–6.1 wt% and 3.9–6.0 wt% NaCl equivalent, respectively. The ore–forming fluids evolved from a CO2–NaCl–H2O ± CH4 to a NaCl–H2O system from stage 1–3. Oxygen, hydrogen, and carbon isotopic data (δ18Ofluid = 1.7‰–8.1‰, δDfluid = –104.1‰ to –91.7‰, δ13Cfluid = –0.4‰–6.3‰) indicate that ore–forming fluids were metamorphic hydrothermal origin with the addition of a late meteoric fluid. Sulfur and lead isotope data for pyrite (δ34Spy = 3.3‰–5.3‰, 206Pb/204Pb = 17.912.3–18.495, 207Pb/204Pb = 15.564–15.590, 208Pb/204Pb = 37.813–38.422) show that the ore–forming materials were mainly derived from diorite and the Ashele Formation. Mineralization, FIs, and isotope studies demonstrate that the Jinba deposit is an orogenic gold deposit.
What Questions Are on the Minds of STEM Undergraduate Students and How Can They Be Addressed?
Authors: Meaders Clara L. , Smith Michelle K. , Boester Timothy , Bracy Anne , Couch Brian A. , Drake Abby G. , Farooq Saima , Khoda Bashir , Kinsland Cynthia , Lane A. Kelly , Lindahl Sarah E. , Livingston William H. , Bundy Ayesha Maliwal , McCormick Amber , Morozov Anya I , Newell-Caito Jennifer L. , Ruskin Katharine J. , Sarvary Mark A. , Stains Marilyne , St. Juliana Justin R. , Thomas Stephanie R. , van Es Cindy , Vinson Erin L. , Vitousek Maren N. , Stetzer Mackenzie R.
Published: February 2021

Addressing common student questions in introductory STEM courses early in the term is one way that instructors can ensure that their students have all been presented with information about how to succeed in their courses. However, categorizing student questions and identifying evidence-based resources to address student questions takes time, and instructors may not be able to easily collect and respond to student questions at the beginning of every course. To help faculty effectively anticipate and respond to student questions, we 1) administered surveys in multiple STEM courses to identify common student questions, 2) conducted a qualitative analysis to determine categories of student questions (e.g., what are best practices for studying, how can in- and out-of- course time be effectively used), and 3) collaboratively identified advice on how course instructors can answer these questions. Here, we share tips, evidence-based strategies, and resources from faculty that instructors can use to develop their own responses for students. We hope that educators can use these common student questions as a starting point to proactively address questions throughout the course and that the compiled resources will allow instructors to easily find materials that can be considered for their own courses.
Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review
Authors: Togashi Keita , Nishitsuka Koichi , Hayashi Shion , Namba Hiroyuki , Goto Sakiko , Takeda Yusuke , Suzuki Shuhei , Kato Tomoya , Yamada Yuki , Konno Eriko , Yoshioka Takashi , Yamakawa Mitsunori , Sonoda Yukihiko , Suzuki Tamio , Yamashita Hidetoshi
Published: February 2021

Background

Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function.

Case Presentation

A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation.

Conclusion

We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.
Lower Baseline Serum Triglyceride Levels Are Associated With Higher Decrease in Body Mass Index After Laparoscopy Sleeve Gastrectomy Among Obese Patients
Authors: Huang Xiu , Li Guifang , Xu Bei , Zhang Junyi , Wang Xingchun , Cheng Xiaoyun , Jayachandran Muthukumaran , Huang Yueye , Qu Shen
Published: February 2021

Aims

To investigate the predictive value of baseline serum triglyceride (TG) levels for improvements of metabolism after laparoscopic sleeve gastrectomy (LSG).

Methods

112 obese patients [body mass index (BMI) ≥ 35 kg/m2] underwent LSG and with complete information of anthropometric and metabolic parameters were divided into normal TG group (group A) and high TG group (group B), while group A had TG levels ≤ 1.7 mmol/L, and group B had TG levels > 1.7 mmol/L. The post-operative changes (Δ) in metabolic parameters between the two groups were compared.

Results

In the whole cohort, the metabolic parameters were significantly improved at 6 months after LSG. BMI and waist circumference (WC) decreased significantly in the two groups. The ΔBMI among group A and group B were 11.42±3.23 vs 9.13±2.77 kg/m2 (p<0.001), respectively. ΔBMI was positively correlated with ΔWC (r=0.696, p<0.001), Δfasting insulin level (r=0.440, p=0.002), Δfasting serum C peptide level (r=0.453, p=0.002), and Δhomeostasis model assessment insulin resistance index (r=0.418, p=0.004) in group A. Compared with group B, group A had a significantly higher odds ratio (OR) of 2.83 (95% confidence interval [CI]1.25–6.38, p=0.012)and 2.73 (95% CI 1.11–6.72, p=0.029) for ΔBMI and ΔWC after adjustment for age and gender, respectively.

Conclusions

Obese patients with baseline TG levels under 1.7 mmol/L had greater loss of weight at six months follow-up later LSG. This finding suggests that baseline TG level may have a predictive value for weight loss, at least in the short-term follow-up.
Design and Performance of a Compact Air-Breathing Jet Hybrid-Electric Engine Coupled With Solid Oxide Fuel Cells
Authors: Ji Zhixing , Qin Jiang , Cheng Kunlin , Liu He , Zhang Silong , Dong Peng
Published: February 2021

A compact air-breathing jet hybrid-electric engine coupled with solid oxide fuel cells (SOFC) is proposed to develop the propulsion system with high power-weight ratios and specific thrust. The heat exchanger for preheating air is integrated with nozzles. Therefore, the exhaust in the nozzle expands during the heat exchange with compressed air. The nozzle inlet temperature is obviously improved. SOFCs can directly utilize the fuel of liquid natural gas after being heated. The performance parameters of the engine are acquired according to the built thermodynamic and mass models. The main conclusions are as follows. 1) The specific thrust of the engine is improved by 20.25% compared with that of the traditional jet engine. As pressure ratios rise, the specific thrust increases up to 1.7 kN/(kg·s−1). Meanwhile, the nozzle inlet temperature decreases. However, the temperature increases for the traditional combustion engine. 2) The power-weight ratio of the engine is superior to that of internal combustion engines and inferior to that of turbine engines when the power density of SOFC would be assumed to be that predicted for 2030. 3) The total pressure recovery coefficients of SOFCs, combustors, and preheaters have an obvious influence on the specific thrust of the engine, and the power-weight ratio of the engine is strongly affected by the power density of SOFCs.
Temporal and Spatial Variations in NDVI and Analysis of the Driving Factors in the Desertified Areas of Northern China From 1998 to 2015
Authors: Wang Xuyang , Li Yuqiang , Wang XinYuan , Li Yulin , Lian Jie , Gong Xiangwen
Published: February 2021

China faces some of the most serious desertification in the world, leading to many problems. To solve them, large-scale ecological restoration projects were implemented. To assess their effectiveness, we analyzed normalized-difference vegetation index (NDVI) data derived from SPOT VEGETATION and gridded climate datasets from 1998 to 2015 to detect the degrees of desertification and the effects of human and climate drivers on vegetation dynamics. We found that NDVI of desertified areas generally decreased before 2000, then increased. The annual increase in NDVI was fixed dunes (0.0013) = semi-fixed dunes (0.0013) > semi-mobile dunes (0.0012) > gobi (gravel) desert (0.0011) > mobile dunes (0.0003) > saline–alkali land (0.0000). The proportions of the area of each desert type in which NDVI increased were fixed dunes (43.4%) > semi-mobile dunes (39.7%) > semi-fixed dunes (26.7%) > saline–alkali land (23.1%) > gobi desert (14.4%) > mobile dunes (12.5%). Thus, the vegetation response to the restoration efforts increased as the initial dune stability increased. The proportion of the area where desertification was dominated by temperature (1.8%) was far less than the area dominated by precipitation (14.1%). However, 67.6% of the change was driven by non-climatic factors. The effectiveness of the ecological restoration projects was significant in the Loess Plateau and in the Mu Us, Horqin, and Hulunbuir sandy lands. In contrast, there was little effect in the Badain Jaran, Ulan Buh, and Tengger deserts; in particular, vegetation cover has declined seriously in the Hunshandake Sandy Land and Alkin Desert Grassland. Thus, more or different ecological restoration must be implemented in these areas.
Spatial Scaling Patterns of Functional Diversity
Authors: Alirezazadeh Saeid , Borges Paulo A. V. , Cardoso Pedro , Gabriel Rosalina , Rigal François , Borda-de-Água Luís
Published: February 2021

Ecology, biogeography and conservation biology, among other disciplines, often rely on species identity, distribution and abundance to perceive and explain patterns in space and time. Yet, species are not independent units in the way they interact with their environment. Species often perform similar roles in networks and their ecosystems, and at least partial redundancy or difference of roles might explain co-existence, competitive exclusion or other patterns reflected at the community level. Therefore, considering species traits, that is, the organisms’ functional properties that interact with the environment, might be of utmost importance in the study of species relative abundances. Several descriptive measures of diversity, such as the species-area relationship (SAR) and the species abundance distribution (SAD), have been used extensively to characterize the communities and as a possible window to gain insight into underlying processes shaping and maintaining biodiversity. However, if the role of species in a community is better assessed by their functional attributes, then one should also study the SAR and the SAD by using trait-based approaches, and not only taxonomic species. Here we merged species according to their similarity in a number of traits, creating functional units, and used these new units to study the equivalent patterns of the SAR and of the SAD (functional units abundance distributions - FUADs), with emphasis on their spatial scaling characteristics. This idea was tested using data on arthropods collected in Terceira island, in the Azorean archipelago. Our results showed that diversity scales differently depending on whether we use species or functional units. If what determines species communities’ dynamics is their functional diversity, then our results suggest that we may need to revaluate the commonly assumed patterns of species diversity and, concomitantly, the role of the underlying processes.
Integrating Causal and Evolutionary Analysis of Life-History Evolution: Arrival Date in a Long-Distant Migrant
Authors: Tomotani Barbara M. , Gienapp Phillip , de la Hera Iván , Terpstra Martijn , Pulido Francisco , Visser Marcel E.
Published: February 2021

In migratory species, the timing of arrival at the breeding grounds is a life-history trait with major fitness consequences. The optimal arrival date varies from year-to-year, and animals use cues to adjust their arrival dates to match this annual variation. However, which cues they use to time their arrival and whether these cues actually predict the annual optimal arrival date is largely unknown. Here, we integrate causal and evolutionary analysis by identifying the environmental variables used by a migratory songbird to time its arrival dates and testing whether these environmental variables also predicted the optimal time to arrive. We used 11 years of male arrival data of a pied flycatcher population. Specifically, we tested whether temperature and normalized difference vegetation index (NDVI) values from their breeding grounds in the Netherlands and from their wintering grounds in Ivory Coast explained the variation in arrival date, and whether these variables correlated with the position of the annual fitness peak at the breeding grounds. We found that temperature and NDVI, both from the wintering and the breeding grounds, explained the annual variation in arrival date, but did not correlate with the optimal arrival date. We explore three alternative explanations for this lack of correlation. Firstly, the date of the fitness peak may have been incorrectly estimated because a potentially important component of fitness (i.e., migration date dependent mortality en route or directly upon arrival) could not be measured. Secondly, we focused on male timing but the fitness landscape is also likely to be shaped by female timing. Finally, the correlation has recently disappeared because climate change disrupted the predictive value of the cues that the birds use to time their migration. In the latter case, birds may adapt by altering their sensitivity to temperature and NDVI.
DHCR7 rs12785878 T>C Polymorphism Is Associated With an Increased Risk of Early Onset of Alzheimer's Disease in Chinese Population
Authors: Liu Xixi , Wu Pengfei , Shen Lu , Jiao Bin , Liao Xinxin , Wang Haochen , Peng Jiangnan , Lin Zhangyuan
Published: February 2021

Background: Vitamin D insufficiency has been considered a risk factor for Alzheimer's disease (AD) in several studies. Recently, four single-nucleotide polymorphisms (SNPs) to be genome-wide significant for 25-hydroxyvitamin D [25(OH)D] were identified to have an association with the risk of AD. These include GC rs2282679 A>C, CYP2R1 rs10741657 T>C, DHCR7 rs12785878 T>C, and CYP24A1 rs6013897 T>A. However, the association between these polymorphisms and AD susceptibility in the Chinese population remains unclear.

Methods: A case-control cohort study was conducted in 676 AD patients (mean age at onset was 69.52 ± 10.90 years, male: 39.2%) and 551 healthy controls (mean age was 67.73 ± 6.02 years, male: 44.8%). Genotyping was determined by PCR and SNaPshot sequencing. To determine whether the four SNPs account for risks in AD in Chinese population, multivariate logistic regression models were performed. Stratified analysis was performed based on gender and age of onset of AD, separately. Statistical significance was set at 0.0125 (0.05/4) based on Bonferroni correction.

Findings:DHCR7 rs12785878 T>C was found to be significantly associated with an increased risk of early-onset Alzheimer's disease (EOAD) (n = 300, risk allele C, adjusted OR = 1.542, adjusted 95% CI = 1.176–2.023, p = 0.002). There was no statistical significance of the other three SNPs between the two groups.

Interpretation: Our results suggested that DHCR7 rs12785878 T>C might be associated with an increased risk of EOAD in the Chinese population, while other polymorphisms related to vitamin D insufficiency might not be. However, due to the limited data in this study, replication studies in a larger sample are required.
Evaluation of a Custom SNP Panel for Identifying and Rectifying of Misjudged Paternity in Deficiency Cases
Authors: Chang Liao , Yu Huiyun , Miao Xinyao , Wen Siqi , Zhang Bao , Li Shengbin
Published: February 2021

Parentage testing is routinely performed by genotyping short tandem repeat (STR) through capillary electrophoresis in the present. However, ambiguous or even misjudged paternity based on STRs happens from time to time in cases where only one putative parent is available. We analyzed STR data of 7,818,969 unrelated pairs and 75 close-relative pairs and found that although the probability of a random false match between non-relatives was 4.22 × 10–6, the incidence of false or ambiguous paternity results between children and first-degree relatives of their true parent was as high as 18.67%. These results highlight the risk of false inclusion of a relative or even non-relatives in parentage testing with STRs. We then validated all ambiguous STR results by targeted sequencing with a custom panel containing 4,830 individual identification single nucleotide polymorphisms (IISNP), found that the ratio of mismatch loci to total SNPs was 1.78–6.95% in close relatives compared with 10.93–13.49% in unrelated pairs. Last, we reported three real cases with undetermined paternity by STRs and rectified them by dissecting with our IISNP panel. These results suggested that high-density IISNP panel can be used to identify and rectify misjudged cases effectively.
Characterization of SALL2 Gene Isoforms and Targets Across Cell Types Reveals Highly Conserved Networks
Authors: Farkas Carlos , Quiroz Aracelly , Alvarez Claudia , Hermosilla Viviana , Aylwin Carlos F. , Lomniczi Alejandro , Castro Ariel F. , Hepp Matias I. , Pincheira Roxana
Published: February 2021

The SALL2 transcription factor, an evolutionarily conserved gene through vertebrates, is involved in normal development and neuronal differentiation. In disease, SALL2 is associated with eye, kidney, and brain disorders, but mainly is related to cancer. Some studies support a tumor suppressor role and others an oncogenic role for SALL2, which seems to depend on the cancer type. An additional consideration is tissue-dependent expression of different SALL2 isoforms. Human and mouse SALL2 gene loci contain two promoters, each controlling the expression of a different protein isoform (E1 and E1A). Also, several improvements on the human genome assembly and gene annotation through next-generation sequencing technologies reveal correction and annotation of additional isoforms, obscuring dissection of SALL2 isoform-specific transcriptional targets and functions. We here integrated current data of normal/tumor gene expression databases along with ChIP-seq binding profiles to analyze SALL2 isoforms expression distribution and infer isoform-specific SALL2 targets. We found that the canonical SALL2 E1 isoform is one of the lowest expressed, while the E1A isoform is highly predominant across cell types. To dissect SALL2 isoform-specific targets, we analyzed publicly available ChIP-seq data from Glioblastoma tumor-propagating cells and in-house ChIP-seq datasets performed in SALL2 wild-type and E1A isoform knockout HEK293 cells. Another available ChIP-seq data in HEK293 cells (ENCODE Consortium Phase III) overexpressing a non-canonical SALL2 isoform (short_E1A) was also analyzed. Regardless of cell type, our analysis indicates that the SALL2 long E1 and E1A isoforms, but not short_E1A, are mostly contributing to transcriptional control, and reveals a highly conserved network of brain-specific transcription factors (i.e., SALL3, POU3F2, and NPAS3). Our data integration identified a conserved molecular network in which SALL2 regulates genes associated with neural function, cell differentiation, development, and cell adhesion between others. Also, we identified PODXL as a gene that is likely regulated by SALL2 across tissues. Our study encourages the validation of publicly available ChIP-seq datasets to assess a specific gene/isoform’s transcriptional targets. The knowledge of SALL2 isoforms expression and function in different tissue contexts is relevant to understanding its role in disease.
The Intersection of the Genetic Architectures of Orofacial Clefts and Normal Facial Variation
Authors: Indencleef Karlijne , Hoskens Hanne , Lee Myoung Keun , White Julie D. , Liu Chenxing , Eller Ryan J. , Naqvi Sahin , Wehby George L. , Moreno Uribe Lina M. , Hecht Jacqueline T. , Long Ross E. , Christensen Kaare , Deleyiannis Frederic W. , Walsh Susan , Shriver Mark D. , Richmond Stephen , Wysocka Joanna , Peeters Hilde , Shaffer John R. , Marazita Mary L. , Hens Greet , Weinberg Seth M. , Claes Peter
Published: February 2021

Unaffected relatives of individuals with non-syndromic cleft lip with or without cleft palate (NSCL/P) show distinctive facial features. The presence of this facial endophenotype is potentially an expression of underlying genetic susceptibility to NSCL/P in the larger unselected population. To explore this hypothesis, we first partitioned the face into 63 partially overlapping regions representing global-to-local facial morphology and then defined endophenotypic traits by contrasting the 3D facial images from 264 unaffected parents of individuals with NSCL/P versus 3,171 controls. We observed distinct facial features between parents and controls across 59 global-to-local facial segments at nominal significance (p ≤ 0.05) and 52 segments at Bonferroni corrected significance (p < 1.2 × 10–3), respectively. Next, we quantified these distinct facial features as univariate traits in another dataset of 8,246 unaffected European individuals and performed a genome-wide association study. We identified 29 independent genetic loci that were associated (p < 5 × 10–8) with at least one of the tested endophenotypic traits, and nine genetic loci also passed the study-wide threshold (p < 8.47 × 10–10). Of the 29 loci, 22 were in proximity of loci previously associated with normal facial variation, 18 were near genes that show strong evidence in orofacial clefting (OFC), and another 10 showed some evidence in OFC. Additionally, polygenic risk scores for NSCL/P showed associations with the endophenotypic traits. This study thus supports the hypothesis of a shared genetic architecture of normal facial development and OFC.
Metabolomic Analysis of Aqueous Humor Identifies Aberrant Amino Acid and Fatty Acid Metabolism in Vogt-Koyanagi-Harada and Behcet’s Disease
Authors: Xu Jing , Su Guannan , Huang Xinyue , Chang Rui , Chen Zhijun , Ye Zi , Cao Qingfeng , Kijlstra Aize , Yang Peizeng
Published: February 2021

To investigate aqueous metabolic profiles in Vogt-Koyanagi-Harada (VKH) and Behcet’s disease (BD), we applied ultra-high-performance liquid chromatography equipped with quadrupole time-of flight mass spectrometry in aqueous humor samples collected from these patients and controls. Metabolite levels in these three groups were analyzed by univariate logistic regression. The differential metabolites were subjected to subsequent pathway analysis by MetaboAnalyst. The results showed that both partial-least squares discrimination analysis and hierarchical clustering analysis showed specific aqueous metabolite profiles when comparing VKH, BD, and controls. There were 28 differential metabolites in VKH compared to controls and 29 differential metabolites in BD compared to controls. Amino acids and fatty acids were the two most abundant categories of differential metabolites. Furthermore, pathway enrichment analysis identified several perturbed pathways, including pantothenate and CoA biosynthesis when comparing VKH with the control group, and D-arginine and D-ornithine metabolism and phenylalanine metabolism when comparing BD with the control group. Aminoacyl-tRNA biosynthesis was altered in both VKH and BD when compared to controls. Our findings suggest that amino acids metabolism as well as two fatty acids, palmitic acid and oleic acid, may be involved in the pathogenesis of BD and VKH.
Breaching the Bacterial Envelope: The Pivotal Role of Perforin-2 (MPEG1) Within Phagocytes
Authors: Merselis Leidy C. , Rivas Zachary P. , Munson George P.
Published: February 2021

The membrane attack complex (MAC) of the complement system and Perforin-1 are well characterized innate immune effectors. MAC is composed of C9 and other complement proteins that target the envelope of gram-negative bacteria. Perforin-1 is deployed when killer lymphocytes degranulate to destroy virally infected or cancerous cells. These molecules polymerize with MAC-perforin/cholesterol-dependent cytolysin (MACPF/CDC) domains of each monomer deploying amphipathic β-strands to form pores through target lipid bilayers. In this review we discuss one of the most recently discovered members of this family; Perforin-2, the product of theMpeg1gene. Since their initial description more than 100 years ago, innumerable studies have made macrophages and other phagocytes some of the best understood cells of the immune system. Yet remarkably it was only recently revealed that Perforin-2 underpins a pivotal function of phagocytes; the destruction of phagocytosed microbes. Several studies have established that phagocytosed bacteria persist and in some cases flourish within phagocytes that lack Perforin-2. When challenged with either gram-negative or gram-positive pathogensMpeg1knockout mice succumb to infectious doses that the majority of wild-type mice survive. As expected by their immunocompromised phenotype, bacterial pathogens replicate and disseminate to deeper tissues ofMpeg1knockout mice. Thus, this evolutionarily ancient gene endows phagocytes with potent bactericidal capability across taxa spanning sponges to humans. The recently elucidated structures of mammalian Perforin-2 reveal it to be a homopolymer that depends upon low pH, such as within phagosomes, to transition to its membrane-spanning pore conformation. Clinical manifestations ofMpeg1missense mutations further highlight the pivotal role of Perforin-2 within phagocytes. Controversies and gaps within the field of Perforin-2 research are also discussed as well as animal models that may be used to resolve the outstanding issues. Our review concludes with a discussion of bacterial counter measures against Perforin-2.
Case Report: Long-Term Response to Pembrolizumab Combined With Endocrine Therapy in Metastatic Breast Cancer Patients With Hormone Receptor Expression
Authors: Wu Dingyong , Tang Shu , Ye Rong , Li Dongmei , Gu Dejian , Chen Rongrong , Zhang Huan , Sun Jianguo , Chen Zhengtang
Published: February 2021

Breast cancer is one of the most commonly diagnosed malignancies. Although endocrine therapy improves the survival of patients with hormone receptor (HR)-positive breast cancer, the post-endocrine therapy strategy for metastatic breast cancer remains challenging. Herein, we report two patients who benefited from antiestrogen agents combined with an immunotherapy regimen to support the notion that an immunotherapy combination regimen may be a potential treatment for patients with HR-positive metastatic breast cancer post-endocrine therapy. Case 1 involved a patient with relapsed breast cancer with ovarian and brain metastases after endocrine therapy. After undergoing surgery for the ovarian lesions, she received three cycles of chemotherapy. Given that the lesions in the brain did not change, chemotherapy was discontinued. A high T cell receptor (TCR) repertoire (high Shannon index and clonality) was observed in the tumor. Considering the patient's preference and safety, and the efficacy of immunotherapy, she was administered with letrozole combined with pembrolizumab. The patient achieved a partial response, and the progression-free survival (PFS) was more than 21 months. Case 2 involved a patient with breast cancer with multiple bone metastases. After failure of combined radiotherapy and chemotherapy, the patient received tamoxifen combined with pembrolizumab based on the patient's preference and clinical biomarkers of a positive differentiation cluster of eight tumor-infiltrating lymphocytes and a high TCR repertoire (high Shannon index and clonality) in the tumor. The patient's bone pain and biomarkers were relieved after the treatment. The patients completed six cycles of pembrolizumab, and the PFS was more than 21 months. In conclusion, our study confirmed that antiestrogen agents combined with an immunotherapy regimen is a promising treatment for patients with HR-positive metastatic breast cancer.