ToTE: A global database on trees of the treeline ecotone.

Globally, treelines form a transition zone between tree-dominated forest downslope and treeless alpine vegetation upslope. Treelines represent the highest boundary of "tree" life form in high-elevation mountains and at high latitudes. Recently, treelines have been shifting upslope in response to climate warming, so it has become important to understand global tree diversity and treeline distributions. However, to the best of our knowledge, no global database on tree flora of treelines exists, which limits our capacity to undertake macroecological analyses. Here, for the first time, we present a global data set on the trees of the treeline ecotone, supported by an online ToTE database. We synthesized the database from 1202 studies published over the last 60 years (1962 to 2022) following the Preferred Reporting Items in Systematic Reviews and Meta-Analysis (PRISMA) protocol. We classified the tree species in the database into three categories: treeline tree (TL) species, near to treeline (NTL) tree species, and tree species with an upper montane range limit (TUMR). The ToTE Version-1 presents a total of 208 tree taxa, including 189 species, five subspecies, and 14 varieties, belonging to 54 genera and 26 families distributed across 34 mountain regions worldwide that either grow exactly at the treeline or have a range limit below the treeline. Of the total taxa, 155, 14, and 39 belong to TL, NTL, and TUMR, respectively. Genera such as Abies, Picea, Pinus, Larix, and Juniperus are more represented in the treeline tree category. On the other hand, Acer, Prunus, Populus, and Quercus have more representatives in the near to treeline category, whereas Erica, Nothofagus, and Polylepis contribute more tree species with an upper montane range limit. Furthermore, families such as Rosaceae and Pinaceae include trees that occur both at the treeline and with an upper montane range limit, whereas Sapindaceae includes trees that occur exclusively near to treeline. Our database also includes information on the global distribution patterns of treeline tree species richness across mountains and biomes. The mountains with the highest number of tree species are the Andes (39) followed by the Himalaya (37). Close to 67% of tree species show restricted distributions in different mountains, with the highest endemism in the Andes and the Himalaya. In terms of tree species distribution, Pinus sylvestris was widespread, with a distribution across nine mountain regions, followed by Picea glauca and Fagus sylvatica, both distributed across five mountain regions. In terms of species' distribution across biomes, the temperate biome harbors the highest treeline tree species richness (152 species), which may reflect the fact that the majority of studies are available from the temperate regions of the world. The remaining 56 species are distributed within five other biomes, with the least in dry tropical and subarctic (four species each). Furthermore, currently 40 treeline tree species fall under different International Union for Conservation of Nature threat categories. We anticipate that our database will help advance research on macroecological, biogeographic, evolutionary, climate-change, and conservation aspects of the treeline on a global scale. The data are released under a Creative Commons Attribution 4.0 international license. Please cite this data paper when the data are reused.

Multifunctional Applications Enabled by Fluorination of Hexagonal Boron Nitride.

2D materials exhibit exceptional properties as compared to their macroscopic counterparts, with promising applications in nearly every area of science and technology. To unlock further functionality, the chemical functionalization of 2D structures is a powerful technique that enables tunability and new properties within these materials. Here, the successful effort to chemically functionalize hexagonal boron nitride (hBN), a chemically inert 2D ceramic with weak interlayer forces, using a gas-phase fluorination process is exploited. The fluorine functionalization guides interlayer expansion and increased polar surface charges on the hBN sheets resulting in a number of vastly improved applications. Specifically, the F-hBN exhibits enhanced dispersibility and thermal conductivity at higher temperatures by more than 75% offering exceptional performance as a thermofluid additive. Dispersion of low volumes of F-hBN in lubricating oils also offers marked improvements in lubrication and wear resistance for steel tribological contacts decreasing friction by 31% and wear by 71%. Additionally, incorporating numerous negatively charged fluorine atoms on hBN induces a permanent dipole moment, demonstrating its applicability in microelectronic device applications. The findings suggest that anchoring chemical functionalities to hBN moieties improves a variety of properties for h-BN, making it suitable for numerous other applications such as fillers or reinforcement agents and developing high-performance composite structures.

Cyclic Wear Reliability of 2D Monolayers.

Understanding wear, a critical factor impacting the reliability of mechanical systems, is vital for nano-, meso-, and macroscale applications. Due to the complex nature of nanoscale wear, the behavior of nanomaterials such as two-dimensional materials under cyclic wear and their surface damage mechanism is yet unexplored. In this study, we used atomic force microscopy coupled with molecular dynamic simulations to statistically examine the cyclic wear behavior of monolayer graphene, MoS2, and WSe2. We show that graphene displays exceptional durability and lasts over 3000 cycles at 85% of the applied critical normal load before failure, while MoS2 and WSe2 last only 500 cycles on average. Moreover, graphene undergoes catastrophic failure as a result of stress concentration induced by local out-of-plane deformation. In contrast, MoS2 and WSe2 exhibit intermittent failure, characterized by damage initiation at the edge of the wear track and subsequent propagation throughout the entire contact area. In addition to direct implications for MEMS and NEMS industries, this work can also enable the optimization of the use of 2D materials as lubricant additives on a macroscopic level.

Angioinvasive mucormycosis in burn intensive care units: A case report and review of literature.

BACKGROUND: Mucormycosis is a rare, rapidly progressive and often fatal fungal infection. The rarity of the condition lends itself to unfamiliarity, delayed treatment, and poor outcomes. Diagnosis of fungal infections early enough to enable appropriate treatment occurs in less than half of affected patients. CASE SUMMARY: An 11-year-old girl with a history of 15% total body surface area scald burns involving both lower limbs progressed to develop angioinvasive mucormycosis. This further led to a thrombosis of the right external iliac artery and vein and rapidly progressive necrosis of surrounding soft tissues. She also had dextrocardia and patent foramen ovale. A right hip disarticulation and serial aggressive debridements were performed but she went on to develop systemic sepsis with multisystem involvement and succumbed to the infection. Pathology revealed mucor species with extensive vascular invasion. CONCLUSION: This case highlights the importance of maintaining vigilance for mycotic infections and acting appropriately when there are signs of fulminant wound infection.

Heterogeneous Rhodium Single-Atom-Site Catalyst Enables Chemoselective Carbene N-H Bond Insertion.

Transition-metal-catalyzed carbene insertion reactions of a nitrogen-hydrogen bond have emerged as robust and versatile methods for the construction of C-N bonds. While significant progress of homogeneous catalytic metal carbene N-H insertions has been achieved, the control of chemoselectivity in the field remains challenging due to the high electrophilicity of the metal carbene intermediates. Herein, we present an efficient strategy for the synthesis of a rhodium single-atom-site catalyst (Rh-SA) that incorporates a Rh atom surrounded by three nitrogen atoms and one phosphorus atom doped in a carbon support. This Rh-SA catalyst, with a catalyst loading of only 0.15 mol %, exhibited exceptional catalytic performance for heterogeneous carbene insertion with various anilines and heteroaryl amines in combination with diazo esters. Importantly, the heterogeneous catalyst selectively transformed aniline derivatives bearing multiple nucleophilic moieties into single N-H insertion isomers, while the popular homogeneous Rh2(OAc)4 catalyst produced a mixture of overfunctionalized side products. Additionally, similar selectivities for N-H bond insertion with a set of stereoelectronically diverse diazo esters were obtained, highlighting the general applicability of this heterogeneous catalysis approach. On the basis of density functional theory calculations, the observed selectivity of the Rh-SA catalyst was attributed to the insertion barriers and the accelerated proton transfer assisted by the phosphorus atom in the support. Overall, this investigation of heterogeneous metal-catalyzed carbene insertion underscores the potential of single-atom-site catalysis as a powerful and complementary tool in organic synthesis.

The role of collagen triple helix repeat containing 1 (CTHRC1) in cancer development and progression.

INTRODUCTION: Collagen triple helix repeat containing 1 (CTHRC1) is a protein that has been implicated in pro-migratory pathways, arterial tissue-repair processes, and inhibition of collagen deposition via the regulation of multiple signaling cascades. Studies have also demonstrated an upregulation of CTHRC1 in multiple cancers where it has been linked to enhanced proliferation, invasion, and metastasis. However, the understanding of the exact role and mechanisms of CTHRC1 in cancer is far from complete. AREAS COVERED: This review focuses on analyzing the role of CTHRC1 in cancer as well as its associations with clinicopathologies and cancer-related processes and signaling. We have also summarized the available literature information regarding the role of CTHRC1 in tumor microenvironment and immune signaling. Finally, we have discussed the mechanisms associated with CTHRC1 regulations, and opportunities and challenges regarding the development of CTHRC1 as a potential target for cancer management. EXPERT OPINION: CTHRC1 is a multifaceted protein with critical roles in cancer progression and other pathological conditions. Its association with lower overall survival in various cancers, and impact on the tumor immune microenvironment make it an intriguing target for further research and potential therapeutic interventions in cancer.

Heavy Metals as Catalysts in the Evolution of Antimicrobial Resistance and the Mechanisms Underpinning Co-selection.

The menace caused by antibiotic resistance in bacteria is acknowledged on a global scale. Concerns over the same are increasing because of the selection pressure exerted by a huge number of different antimicrobial agents, including heavy metals. Heavy metals are non-metabolizable and recalcitrant to degradation, therefore the bacteria can expel the pollutants out of the system and make it less harmful via different mechanisms. The selection of antibiotic-resistant bacteria may be influenced by heavy metals present in environmental reservoirs. Through co-resistance and cross-resistance processes, the presence of heavy metals in the environment can act as co-selecting agents, hence increasing resistance to both heavy metals and antibiotics. The horizontal gene transfer or mutation assists in the selection of mutant bacteria resistant to the polluted environment. Hence, bioremediation and biodegradation are sustainable methods for the natural clean-up of pollutants. This review sheds light on the occurrence of metal and antibiotic resistance in the environment via the co-resistance and cross-resistance mechanisms underpinning co-selection emphasizing the dearth of studies that specifically examine the method of co-selection in clinical settings. Furthermore, it is advised that future research incorporate both culture- and molecular-based methodologies to further our comprehension of the mechanisms underlying bacterial co- and cross-resistance to antibiotics and heavy metals.

Tunable 2D Conjugated Porous Organic Polymer Films for Precise Molecular Nanofiltration and Optoelectronics.

Structural design of 2D conjugated porous organic polymer films (2D CPOPs), by tuning linkage chemistries and pore sizes, provides great adaptability for various applications, including membrane separation. Here, four free-standing 2D CPOP films of imine- or hydrazone-linked polymers (ILP/HLP) in combination with benzene (B-ILP/HLP) and triphenylbenzene (TPB-ILP/HLP) aromatic cores are synthesized. The anisotropic disordered films, composed of polymeric layered structures, can be exfoliated into ultrathin 2D-nanosheets with layer-dependent electrical properties. The bulk CPOP films exhibit structure-dependent optical properties, triboelectric nanogenerator output, and robust mechanical properties, rivaling previously reported 2D polymers and porous materials. The exfoliation energies of the 2D CPOPs and their mechanical behavior at the molecular level are investigated using density function theory (DFT) and molecular dynamics (MD) simulations, respectively. Exploiting the structural tunability, the comparative organic solvent nanofiltration (OSN) performance of six membranes having different pore sizes and linkages to yield valuable trends in molecular weight selectivity is investigated. Interestingly, the OSN performances follow the predicted transport modeling values based on theoretical pore size calculations, signifying the existence of permanent porosity in these materials. The membranes exhibit excellent stability in organic solvents at high pressures devoid of any structural deformations, revealing their potential in practical OSN applications.

Antibacterial Efficacy of Mineral Trioxide Aggregate, Bioactive Glass and Epoxy-Resin Based Sealer: An In-Vitro Interventional Study.

Aim: The aim and objective of this in vitro study was to evaluate the antibacterial efficacy of mineral trioxide aggregate, bioactive glass sealer, and epoxy-resin-based sealer. Materials and Methods: In the present study, 22 Mueller Hinton agar (MH agar) plates were employed and equally divided into two groups. Three holes were made by removal of agar at equidistant points and filled with root canal sealers. The strains of the bacteria used in this study were S. aureus (ATCC 6538) and C. albicans (ATCC 10231) and were divided into two groups and root canal sealers were divided into three subgroups: mineral trioxide aggregate (MTA) fillapex Sealer, Nishika Bioactive Glass sealer, and Syntex Epoxy Resin base sealer. For Staphylococcus aureus, peptone water was placed in a 2 mL test tube and bacteria were extracted from blood agar plates using a nichrome wire loop and poured into the peptone water-containing test tube and incubated for 2 hours and for C. albicans, fungi were grown at 37°C for 24 hours in MH Broth and seeded into MH agar to produce turbidity of 0.5 on the McFarland scale, which corresponds to a concentration of 108 CFU/mL. This MH broth was used as a second layer. The seeded agar was then added over the plates immediately after the insertion of sealer cement. After incubation, the diameters of zones of inhibition around the plates were measured. Results: The results of this study showed that the highest inhibition was recorded in Syntex sealer against Staphylococcus aureus followed by MTA fillapex sealer and Nishika sealer, whereas MTA fillapex showed the highest inhibition against C. albicans followed by Syntex sealer and Nishika sealer. Conclusion: Syntex sealer exhibits better antibacterial efficacy against Staphylococcus aureus and MTA fillapex exhibit better antibacterial efficacy against C. albicans.

Evaluating the Emergency Surgery Score (ESS) in Predicting Postoperative Outcomes Following Emergency Laparotomy: Insights From an Indian Tertiary Center.

AIMS AND OBJECTIVES:  To determine the predictive value of Emergency Surgery Score (ESS) with regard to mortality and morbidity rates of patients undergoing emergency laparotomy. METHOD: The ESS ranging from 0 to 29 is an extensive risk calculator based on 22 variables including important parameters like demographics, preoperative treatment, comorbidities, and laboratory values. Twenty patients who underwent emergency laparotomy were preoperatively assessed and ESS was calculated for each. After establishment of diagnosis and resuscitation, the patient was taken up for emergency laparotomy. Postoperatively, patients were monitored clinically as well as with laboratory and radiological investigations as per case needed till discharge and further followed up physically in OPD/ward or interviewed telephonically for 30 days on a weekly basis. Incidence of mortality and morbidity in terms of postoperative complications, ICU admission, reoperation and readmission among the cases occurring within 30 days of procedure were recorded. RESULTS: ESS correlated well with the outcome in the current study, 10 out of 14 patients with score less than 8 were discharged without any complications. Mean ESS was higher among non-survivors. Ability of ESS to predict postoperative mortality, morbidity and ICU stay was proven statistically with c-statistics of 0.853, 0.84, 0.879 respectively. ESS was found to be a good predictor for the development of postoperative lower respiratory tract infection (LRTI) (c-statistic=0.828), sepsis (c-statistic=0.867), disseminated intravascular coagulation (DIC) (c-statistic=0.805), acute kidney injury (AKI) (c-statistic=0.804). ESS showed poor correlation with reoperation and readmission rates. CONCLUSION: The current study underscores the critical importance of employing risk stratification through ESS for patients undergoing emergency laparotomy. By employing ESS, healthcare professionals can accurately anticipate resuscitation requirements and stabilize patients preoperatively. This proactive approach enables the identification and optimization of patients unsuitable for immediate surgery, facilitating informed decisions on targeted treatment, surgical intervention, and postoperative care pathways.

Vacancy-Enhanced Sb-N4 Sites for the Oxygen Reduction Reaction and Zn-Air Battery.

With the advantages of a Fenton-inactive characteristic and unique p electrons that can hybridize with O2 molecules, p-block metal-based single-atom catalysts (SACs) for the oxygen reduction reaction (ORR) have tremendous potential. Nevertheless, their undesirable intrinsic activity caused by the closed d10 electronic configuration remains a major challenge. Herein, an Sb-based SAC featuring carbon vacancy-enhanced Sb-N4 active centers, corroborated by the results of high-angle annular dark-field scanning transmission electron microscopy and X-ray absorption fine structure, has been developed for an incredibly effective ORR. The obtained SbSA-N-C demonstrates a positive half-wave potential of 0.905 V and excellent structural stability in alkaline environments. Density functional theory calculations reveal that the carbon vacancies weaken the adsorption between Sb atoms and the OH* intermediate, thus promoting the ORR performance. Practically, the SbSA-N-C-based Zn-air batteries achieve impressive outcomes, such as a high power density of 181 mW cm-2, showing great potential in real-world applications.

Construction of heterogeneous interfaces for water activation and dissociation to synergistically boost overall water splitting.

Construction of heterogeneous interfaces with dual active components to synergistically promote both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is an effective strategy for facilitating electrochemical water splitting, but the appropriate active component regulation via simple synthesis procedures is still challenging. Herein, the Co and Co2Mo3O8 active components are screened to construct effective heterogeneous interfaces and successfully integrated on Ni foam by thermal reduction of cobalt molybdate precursor. And this bifunctional electrode (Co/Co2Mo3O8/NF) required overpotentials of only 164 and 360 mV to drive the 100 mA cm-2 for HER and OER in alkaline media, respectively. Theoretical calculations showed that the electron transfer occurred from Co to Co2Mo3O8 at the interface, then the formed interfacial cobalt atoms with deficient electron were beneficial for water activation, and reduced energy barrier of water dissociation under the synergistic effect of Co2Mo3O8. Notably, the alkaline electrolyzer based on symmetric Co/Co2Mo3O8/NF electrodes generated 100 mA cm-2 at a voltage of only 1.75 V, surpassing commercially available precious-metal Pt/RuO2-based catalysts.

Synergistic Ni-W Dimer Sites Induced Stable Compressive Strain for Boosting the Performance of Pt as Electrocatalyst for the Oxygen Reduction Reaction.

Alloying Pt catalysts with transition metal elements is an effective pathway to enhance the performance of oxygen reduction reaction (ORR), but often accompanied with severe metal dissolution issue, resulting in poor stability of alloy catalysts. Here, instead of forming traditional alloy structure, we modify Pt surface with a novel Ni-W dimer structure by the atomic layer deposition (ALD) technique. The obtained NiW@PtC catalyst exhibits superior ORR performance both in liquid half-cell and practical fuel cell compared with initial Pt/C. It is discovered that strong synergistic Ni-W dimer structure arising from short atomic distance induced a stable compressive strain on the Pt surface, thus boosting Pt catalytic performance. This surface modification by synergistic dimer sites offers an effective strategy in tailoring Pt with excellent activity and stability, which provides a significant perspective in boosting the performance of commercial Pt catalyst modified with polymetallic atom sites.

The Crucial Role of Molecular Biology in Cancer Therapy: A Comprehensive Review.

Molecular biology shines a light of hope amid the complex terrain of cancer, bringing revolutionary approaches to cancer treatment. Instead of providing a synopsis, this review presents an engaging story that sheds light on the genetic nuances controlling the course of cancer. This review goes beyond just listing genetic alterations to examine the complex interactions that lead to oncogene activation, exploring particular triggers such as viral infections or proto-oncogene mutations. A comprehensive grasp of the significant influence of oncogenes is possible through the classification and clarification of their function in various types of cancer. Furthermore, the role of tumor suppressor genes in controlling cell division and preventing tumor growth is fully explained, providing concrete examples and case studies to ground the conversation and create a stronger story. This study highlights the practical applications of molecular biology and provides a comprehensive overview of various detection and treatment modalities. It emphasizes the effectiveness of RNA analysis, immunohistochemistry, and next-generation sequencing (NGS) in cancer diagnosis and prognosis prediction. Examples include the individualized classification of breast cancers through RNA profiling, the use of NGS to identify actionable mutations such as epidermal growth factor receptor and anaplastic lymphoma kinase in lung cancer, and the use of immunohistochemical staining for proteins such as Kirsten rat sarcoma viral oncogene to guide treatment decisions in colorectal cancer. This paper carefully examines how molecular biology is essential to creating new strategies to fight this difficult and widespread illness. It highlights the exciting array of available therapeutic approaches, offering concrete instances of how clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR-Cas9), targeted pharmaceuticals, immunotherapy, and treatments that induce apoptosis are driving a paradigm shift in cancer care. The revolutionary CRISPR-Cas9 system takes center stage, showcasing how precise gene editing could transform cancer therapy. This study concludes by fervently highlighting the critical role that molecular biology plays in reducing the complexity of cancer and changing the treatment landscape. It lists accomplishments but also thoughtfully examines cases and findings that progress our search for more precisely customized and effective cancer therapies.

Chemo-mechanical failure mechanisms of the silicon anode in solid-state batteries.

Silicon is a promising anode material due to its high theoretical specific capacity, low lithiation potential and low lithium dendrite risk. Yet, the electrochemical performance of silicon anodes in solid-state batteries is still poor (for example, low actual specific capacity and fast capacity decay), hindering practical applications. Here the chemo-mechanical failure mechanisms of composite Si/Li6PS5Cl and solid-electrolyte-free silicon anodes are revealed by combining structural and chemical characterizations with theoretical simulations. The growth of the solid electrolyte interphase at the Si|Li6PS5Cl interface causes severe resistance increase in composite anodes, explaining their fast capacity decay. Solid-electrolyte-free silicon anodes show sufficient ionic and electronic conductivities, enabling a high specific capacity. However, microscale void formation during delithiation causes larger mechanical stress at the two-dimensional interfaces of these anodes than in composite anodes. Understanding these chemo-mechanical failure mechanisms of different anode architectures and the role of interphase formation helps to provide guidelines for the design of improved electrode materials.

Imine-Linked 2D Conjugated Porous Organic Polymer Films for Tunable Acid Vapor Sensing.

Two-dimensional (2D) films of conjugated porous organic polymers (C-POPs) can translate the rich in-plane functionalities of conjugated frameworks into diverse optical and electronic applications while addressing the processability issues of their crystalline analogs for adaptable device architectures. However, the lack of facile single-step synthetic routes to obtain large-area high-quality films of 2D-C-POPs has limited their application possibilities so far. Here, we report the synthesis of four mechanically robust imine-linked 2D-C-POP free-standing films using a single-step fast condensation route that is scalable and tunable. The rigid covalently bonded 2D structures of the C-POP films offer high stability for volatile gas sensing in harsh environments while simultaneously enhancing site accessibility for gas molecules due to mesoporosity by structural design. Structurally, all films were composed of exfoliable layers of 2D polymeric nanosheets (NSs) that displayed anisotropy from disordered stacking, evinced by out-of-plane birefringent properties. The tunable in-plane conjugation, different nitrogen centers, and porous structures allow the films to act as ultraresponsive colorimetric sensors for acid sensing via reversible imine bond protonation. All the films could detect hydrogen chloride (HCl) gas down to 0.05 ppm, far exceeding the Occupational Safety and Health Administration's permissible exposure limit of 5 ppm with fast response time and good recyclability. Computational insights elucidated the effect of conjugation and tertiary nitrogen in the structures on the sensitivity and response time of the films. Furthermore, we exploited the exfoliated large 2D NSs and anisotropic optoelectronic properties of the films to adapt them into micro-optical and triboelectric devices to demonstrate their real-time sensing capabilities.

Unusual Sabatier principle on high entropy alloy catalysts for hydrogen evolution reactions.

The Sabatier principle is widely explored in heterogeneous catalysis, graphically depicted in volcano plots. The most desirable activity is located at the peak of the volcano, and further advances in activity past this optimum are possible by designing a catalyst that circumvents the limitation entailed by the Sabatier principle. Herein, by density functional theory calculations, we discovered an unusual Sabatier principle on high entropy alloy (HEA) surface, distinguishing the "just right" (ΔGH* = 0 eV) in the Sabatier principle of hydrogen evolution reaction (HER). A new descriptor was proposed to design HEA catalysts for HER. As a proof-of-concept, the synthesized PtFeCoNiCu HEA catalyst endows a high catalytic performance for HER with an overpotential of 10.8 mV at -10 mA cm-2 and 4.6 times higher intrinsic activity over the state-of-the-art Pt/C. Moreover, the unusual Sabatier principle on HEA catalysts can be extended to other catalytic reactions.

Role of PLK1/NUMB/NOTCH in epithelial-mesenchymal transition in human melanoma.

Polo-like kinase 1 (PLK1), a serine/threonine kinase, is overexpressed in melanoma and its expression has been associated with poor disease prognosis. PLK1 has been shown to interact with NUMB, a NOTCH antagonist. However, the exact role of PLK1, NUMB, and NOTCH signaling in epithelial-mesenchymal transition (EMT) in melanoma progression is unclear. In this study, Affymetrix microarray analysis was performed to determine differentially expressed genes following shRNA-mediated knockdown of PLK1 in human melanoma cells that showed significant modulations in EMT and metastasis-related genes. Using multiple PLK1-modulated melanoma cell lines, we found that PLK1 is involved in the regulation of cell migration, invasion, and EMT via its kinase activity and NOTCH activation. In vitro kinase assay and mass spectrometry analysis demonstrated a previously unknown PLK1 phosphorylation site (Ser413) on NUMB. Overexpression of non-phosphorylatable (S413A) and phosphomimetic (S413D) mutants of NUMB in melanoma cells implicated the involvement of NUMB-S413 phosphorylation in cell migration and invasion, which was independent of NOTCH activation. To determine the clinical relevance of these findings, immunohistochemistry was performed using melanoma tissue microarray, which indicated a strong positive correlation between PLK1 and N-cadherin, a protein required for successful EMT. These findings were supported by TCGA analysis, where expression of high PLK1 with low NUMB or high NOTCH or N-cadherin showed a significant decrease in survival of melanoma patients. Overall, these results suggest a potential role of PLK1 in EMT, migration, and invasion of melanoma cells. Our findings support the therapeutic targeting of PLK1, NUMB, and NOTCH for melanoma management.

Modern pollen dispersal in relation to present vegetation distribution and land use in the Baspa valley, Kinnaur, western Himalayas.

Interpretation of a fossil pollen data for the vegetation and climate reconstruction of any region needs a modern pollen-vegetation analogue for its calibration. We analyzed the surface sediments and moss polsters for the pollen and microcharcoal records to understand the modern pollen-vegetation relationship and human activities in the Baspa Valley, Kinnaur, Himachal Pradesh. Presently, valley is occupied by the arboreal and non-arboreal vegetation of temperate to subalpine habitats and land use activities. The recovered pollen assemblages showed variability in the dispersal behavior of pollen of taxa growing along the valley transect and also captured the signals of human activities over land use. The overall dominance of arboreal pollen in the recovered pollen assemblage corresponds with the dominant growth of conifers and broadleaf tree taxa and represents the valley vegetation at a regional scale. However, the profuse pollen production of a few arboreal taxa and long distance pollen transport from one vegetation zone to other by the strong upthermic valley winds could bias the pollen representation of in-situ vegetation. The high pollen frequency of non-arboreal taxa in the open meadows represents the near vicinity to their plant source. Human activities like fire burning and cultivation by the local population are evident by the recovery of microcharcoal particles and pollen of plants belonging to Cerealia Poaceae, Asteraceae, Amaranthaceae, Polygonaceae, Rosaceae, Juglandaceae, etc. The dataset taken as modern pollen-vegetation analogue is useful to assess past changes in the vegetation and land cover in relation to climate and human factors for future sustenance.