Effects of climate change on the potential distribution of the threatened relict Dipentodon sinicus of subtropical forests in East Asia: Recommendations for management and conservation

Dipentodon sinicus Dunn. (Dipentodonaceae) is a rare and threatened relict plant species usually found co-dominating with other relict plants in subtropical forest patches in highly fragmented habitats of southwestern China, northern Vietnam and northeastern Myanmar of East Asia. To date, its management and conservation strategies in the light of climate change have not been explored. We evaluated effects of climate change on the distribution of climatically suitable areas of D. sinicus as found prevailing during the last glacial maximum (LGM), the mid-Holocene and the present time, and predicted the distribution of climatically suitable habitats in 2070 throughout East Asia. The results as derived from ecological niche modeling (ENM) show the current distribution to be limited to the prehistoric (the mid-Holocene and LGM) refugia, and to indicate decreasing probability of presence and a reducing range of distribution for 2070. In addition, the suitable areas predicted with high probability (0.5–1) only account for on average 9.8% of the total area of potential habitats (threshold‒1) among the models for the year 2070, thereby indicating that D. sinicus is highly vulnerable. Under all the future scenarios for the year 2070, 69–74.2% of potential habitats in China would be outside protected areas. We assess and propose priorities for protected areas, and provide suggestions for conservation management strategies.This study received financial support from Science and Technology Department of Yunnan University, China (2019YNU002), the Ministry of Science and Technology of China (2015FY210200-15), Ajuts a Grups de Recerca Consolidats” (grants nos. 2014-SGR514-GREB and 2017-SGR1116) from the Generalitat de Catalunya (Spain), Applied Basic Research Foundation of Yunnan Province, China (Grant No. 2019FB058), the Environment Research and Technology Development Fund (JPMEERF15S11407) of the Environmental Restoration and Conservation Agency of Japan, and the Kakenhi Grant Number 15H02833.Highlights Abstract Keywords 1. Introduction 2. Material and methods 2.1. Species 2.2. Occurrence data and ecological niche modeling 3. Results 3.1. Model performance and present potential distribution 3.2. Projected distribution during the mid-Holocene (ca. 6000 yr BP) and LGM (ca. 21,000 yr BP) 3.3. Projected distribution under future climate (2070) 4. Discussion 4.1. Effects of climate change on spatial distribution patterns of D. sinicus 5. Recommendations for future conservation efforts and management Declaration of competing interest Acknowledgements Appendix A. Supplementary data Reference

Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with relapsed/refractory TCL and NKTL were treated with standard dose ICE, dexamethasone 20 mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose levels (DL) 1, 2 and 3 were 40, 60 and 80 mg, respectively. Eleven patients with a median age of 60 years were enrolled; six at DL1 and five at DL2. Patients had received a median of two (range, 1-4) prior lines of treatment and seven had primary refractory disease at entry into the study. Patients received a median of three cycles (range, 1-6) of selinexor-DICE. The most common grade 1 or 2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common grade 3 or 4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed dose-limiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the ten evaluable patients, the overall and complete response rates were 91% and 82%, respectively. The maximum tolerated dose of selinexor was 40 mg when combined with DICE. The combination showed promising complete response rates in patients with relapsed/refractory TCL and NKTL but was poorly tolerated. (clinicaltrials. gov identifier: NCT03212937)

Identifying long-term stable refugia for dominant Castanopsis species of evergreen broad-leaved forests in East Asia: A tool for ensuring their conservation

Identifying and protecting refugia is a priority for conservation management under projected anthropogenic climate change. We have two main objectives: the first is to explore the spatial (East Asia) and temporal (Last Glacial Maximum to year 2070) distribution patterns of dominant Castanopsis species of evergreen broad-leaved forests, also the relation with their niche breadths; the second is to identify long-term stable refugia for preserving these species and provide a framework of conservation strategies. We find that there is an extraordinary richness with 32 dominant Castanopsis species, and they form both a geographically and climatically almost unbroken connection from ca. 5°N to 38°N, having thus ecological significance. During the Mid-Holocene and, particularly, the Last Glacial Maximum, the predicted suitable areas of the species as a whole were larger than those in the present. By 2070, potentially suitable areas with high richness of dominant Castanopsis species will be reduced by 94.5 % on average. No correlation between species niche breadths and distribution ranges is found, which could be due to regional climate stability. Mountains of southwestern and southern Yunnan in China are identified as climatically long-term stable refugia for 7¿9 Castanopsis species. We recommend that these refugia have the highest priority of conservation to prevent their extinction. Our suggested urgent measures include improving the effectiveness of currently protected Castanopsis species and expanding the network of protected areas to cover a larger fraction of the refugia, as well as ensuring Castanopsis species natural regeneration potential in fragmented and natural secondary forest areas.This study received financial support from the Major Program for Basic Research Project of Yunnan Province, China (202101BC070002), the Science and Technology Department of Yunnan University, China (2019YNU002), the Ministry of Science and Technology of China (2015FY210200-15), the Spanish Ministry of Science and Innovation (grant PID2020-119163GB-I00 funded by MCIN/AEI/10.13039/501100011033), the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency of Japan (JPMEERF20202002), and the Northeastern Research Institute of Petrified Wood and Mineral Resources, Nakhon Ratchasima Rajabhat University, Thailand.Keywords 1. Introduction 2. Materials and methods 2.1. Data collection and notations 2.2. Ecological niche modeling 2.3. Data analyses 3. Results 3.1. Dominant Castanopsis species in East Asia today: richness and distribution patterns 3.2. Richness of dominant Castanopsis species shaped by climate change 3.3. Niche groups and niche breadths of dominant Castanopsis species 3.4. Climatically long-term stable refugia 4. Discussion 4.1. Richness of dominant Castanopsis species shaped by climate change 4.2. Niche groups and niche breadths of dominant Castanopsis species 4.3. Long-term stable refugia and conservation strategies 5. Conclusions CRediT authorship contribution statement Declaration of competing interest Acknowledgements Appendix A. Supplementary material Reference

The relationship between niche breadth and range size of beech (Fagus) species worldwide

Aim: This work explores whether the commonly observed positive range size–niche breadth relationship exists for Fagus, one of the most dominant and widespread broad-leaved deciduous tree genera in temperate forests of the Northern Hemisphere. Additionally, we ask whether the 10 extant Fagus species’ niche breadths and climatic tolerances are under phylogenetic control. Location: Northern Hemisphere temperate forests. Taxon: Fagus L. Methods: Combining the global vegetation database sPlot with Chinese vegetation data, we extracted 107,758 relevés containing Fagus species. We estimated biotic and climatic niche breadths per species using plot-based co-occurrence data and a resource-based approach, respectively. We examined the relationships of these estimates with range size and tested for their phylogenetic signal, prior to which a Random Forest (RF) analysis was applied to test which climatic properties are most conserved across the Fagus species. Results: Neither biotic niche breadth nor climatic niche breadth was correlated with range size, and the two niche breadths were incongruent as well. Notably, the widespread North American F. grandifolia had a distinctly smaller biotic niche breadth than the Chinese Fagus species (F. engleriana, F. hayatae, F. longipetiolata and F. lucida) with restricted distributions in isolated mountains. The RF analysis revealed that cold tolerance did not differ among the 10 species, and thus may represent an ancestral, fixed trait. In addition, neither biotic nor climatic niche breadths are under phylogenetic control. Main Conclusions: We interpret the lack of a general positive range size–niche breadth relationship within the genus Fagus as a result of the widespread distribution, high among-region variation in available niche space, landscape heterogeneity and Quaternary history. The results hold when estimating niche sizes either by fine-scale co-occurrence data or coarse-scale climate data, suggesting a mechanistic link between factors operating across spatial scales. Besides, there was no evidence for diverging ecological specialization within the genus Fagus

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Identifying long-term stable refugia for dominant Castanopsis species of evergreen broad-leaved forests in East Asia: a tool for ensuring their conservation

Identifying and protecting refugia is a priority for conservation management under projected anthropogenic climate change. We have two main objectives: the first is to explore the spatial (East Asia) and temporal (Last Glacial Maximum to year 2070) distribution patterns of dominant Castanopsis species of evergreen broad-leaved forests, also the relation with their niche breadths; the second is to identify long-term stable refugia for preserving these species and provide a framework of conservation strategies. We find that there is an extraordinary richness with 32 dominant Castanopsis species, and they form both a geographically and climatically almost unbroken connection from ca. 5°N to 38°N, having thus ecological significance. During the Mid-Holocene and, particularly, the Last Glacial Maximum, the predicted suitable areas of the species as a whole were larger than those in the present. By 2070, potentially suitable areas with high richness of dominant Castanopsis species will be reduced by 94.5 % on average. No correlation between species niche breadths and distribution ranges is found, which could be due to regional climate stability. Mountains of southwestern and southern Yunnan in China are identified as climatically long-term stable refugia for 7–9 Castanopsis species. We recommend that these refugia have the highest priority of conservation to prevent their extinction. Our suggested urgent measures include improving the effectiveness of currently protected Castanopsis species and expanding the network of protected areas to cover a larger fraction of the refugia, as well as ensuring Castanopsis species natural regeneration potential in fragmented and natural secondary forest areas

Community Structure and Survival of Tertiary Relict Thuja sutchuenensis (Cupressaceae) in the Subtropical Daba Mountains, Southwestern China.

A rare coniferous Tertiary relict tree species, Thuja sutchuenensis Franch, has survived in the Daba Mountains of southwestern China. It was almost eliminated by logging during the past century. We measured size and age structures and interpreted regeneration dynamics of stands of the species in a variety of topographic contexts and community associations. Forest communities containing T. sutchuenensis were of three types: (1) the Thuja community dominated by T. sutchuenensis, growing on cliffs; (2) the Thuja-Quercus-Cyclobalanopsis community dominated by T. sutchuenensis, Quercus engleriana and Cyclobalanopsis oxyodon, along with Fagus engleriana and Carpinus fargesiana, on steep slopes; (3) the Thuja-Tsuga-Quercus community dominated by T. sutchuenensis, Tsuga chinensis, and Quercus spinosa, on crest ridges. The established seedlings/saplings were found in limestone crevices, on scarred cliff-faces, cliff-edges, fallen logs, canopy gaps and forest margins. The radial growth rate was 0.5-1.1 mm per year. Its growth forms were distorted. It had strong sprouting ability after disturbances. The T. sutchuenensis population thrives on cliffs where there is little competition from other species because of harsh conditions and rockslide disturbances. It is shade-intolerant but stress-tolerant. Its regeneration has depended on natural disturbances

Ecological niche modeling applied to the conservation of the East Asian relict endemism Glyptostrobus pensilis (Cupressaceae)

Glyptostrobus pensilis (Cupressaceae) is the only surviving species of the genus Glyptostrobus. Although the species is widely cultivated throughout China, in the wild it only occurs as small stands in southeastern China, central Laos, and southern Vietnam. However, its low genetic variability, lack of recruitment, and the progressive destruction of its habitat caused by humans, have meant that the populations are showing a clear declining trend and the species as a whole is threatened. Ecological niche modeling is used here to study the present potential distribution, as well as in the future (2061–2080) using several global circulation models under two of the shared socioeconomic pathways (SSP 126 and SSP 585) that are being used to produce the IPCC Sixth Assessment Report. The current potential area of G. pensilis is of 1,452,481 km with the areas of greatest probability of presence located in southeastern China. This potential area is reduced for the future according to most models, with greater losses for the SSP 585 scenario. Between 6.9 and 31.3% of all wild populations of G. pensilis would be outside potential areas (including the Lao populations, which harbor the highest levels of genetic variability). Conservation measures include the expansion of the current network of protected areas (since over 90% of wild populations do not occur within them), the development of propagation techniques, and the carrying out of translocation activities that should require international collaboration among the countries in which the species is found. With the current knowledge, we have reassessed the threat status of the species under the IUCN criteria, downgrading it from CR to EN both for China and at global level.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study received financial support from the Science and Technology Department of Yunnan Province, China [the Major Program for Basic Research Project of Yunnan Province, China (202101BC070002)], the Science and Technology Department of Yunnan University, China (2019YNU002), the Ministry of Science and Technology of China [the Special Foundation for National Science and Technology Basic Resources Investigation of China (2015FY210200-15)], the Spanish Ministerio de Ciencia e Innovación (project PID2020-119163 GB-I00 funded by MCIN/AEI/10. 13039/ 501100011033), and by the Environment Research and Technology Development Fund (JPMEERF20202002) of the Environmental Restoration and Conservation Agency of Japan.Abstract Introduction Materials and methods Study species Study area Ecological variables and ecological niche modeling (ENM) Protected areas IUCN threat categories Results Current and future potential distribution of G. pensilis Conservation aspects of G. pensilis Discussion Modeling of ecological niche and current potential area of G. pensilis Effects of climate change on the potential future (2061–2080) distribution of G. pensilis Conservation issues of G. pensilis: threat category reassessment, protected areas, and suggestions Conclusions Data availability References Funding Author information Ethics declarations Additional information Supplementary Information Rights and permissions About this articlePeer reviewe