Explore the vast range of titles available.

\"This is awkward: you greet an acquaintance you haven't seen for a while. One of you goes in for a hug; the other initially offers a handshake, then leans in, by which time the hugger is hesitating. In the end, you both do a half-hearted back pat, and then settle into stilted small talk. Variation: suppose the friend is one from who you've been estranged- your last encounter ended in a falling-out, but that was some time ago, and you haven't spoken since. Does this make things more awkward? This is awkward, too: you're a graduate student having dinner with a distinguished visiting speaker who wants to hear more about your research. Suddenly, as you're talking, a piece of food flies out of your mouth and lands on their pristine black sweater. Did they see it? Do they know? They must know. But there's no acknowledgement; you try not to stare at it, and continue the interaction, saying nothing. And this is awkward: someone you consider a friend is engaging in inappropriate flirting at work. They've been going to bars with subordinates after work, and even hooked up with one or two. You think this is sexual harassment, and you know you should talk to them about it, but you can't seem to figure out how to have the conversation\"-- Provided by publisher.

W listopadzie 2016 r. Instytut Niskich Temperatur i Badań Strukturalnych PAN obchodził uroczyście 50-lecie swojego istnienia. Przedstawiony został zarys historii kilkunastu lat wcześniejszego istnienia dziesięciu placówek naukowych, z których ostatecznie w 1966 r. powstał Instytut. Pokazano zmagania profesorów Romana Ingardena i Włodzimierza Trzebiatowskiego o utworzenie we Wrocławiu silnego ośrodka fizyki i fizykochemii ciała stałego.Institute of Low Temperature and Structure Research of Polish Academy of Sciences celebrated its 50th anniversary in November 2016. The paper presents the history of the Institute going backward to the history of other ten scientific institutions from which the Institute was finally founded in 1966. It shows the efforts of Prof. Roman Ingarden and Prof. Włodzimierz Trzebiatowski to establish a powerful center of physics and physico-chemistry of solid state in Wrocław.

The neuronal PAS domain proteins NPAS1 and NPAS3 are members of the basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) family, and their genetic deficiencies are linked to a variety of human psychiatric disorders including schizophrenia, autism spectrum disorders and bipolar disease. NPAS1 and NPAS3 must each heterodimerize with the aryl hydrocarbon receptor nuclear translocator (ARNT), to form functional transcription complexes capable of DNA binding and gene regulation. Here we examined the crystal structures of multi-domain NPAS1-ARNT and NPAS3-ARNT-DNA complexes, discovering each to contain four putative ligand-binding pockets. Through expanded architectural comparisons between these complexes and HIF-1α-ARNT, HIF-2α-ARNT and CLOCK-BMAL1, we show the wider mammalian bHLH-PAS family is capable of multi-ligand-binding and presents as an ideal class of transcription factors for direct targeting by small-molecule drugs. Transcription factors are proteins that can bind to DNA to regulate the activity of genes. One family of transcription factors in mammals is known as the bHLH-PAS family, which consists of sixteen members including NPAS1 and NPAS3. These two proteins are both found in nerve cells, and genetic mutations that affect NPAS1 or NPAS3 have been linked to psychiatric conditions in humans. Therefore, researchers would like to discover new drugs that can bind to these proteins and control their activities in nerve cells. Understanding the three-dimensional structure of a protein can aid the discovery of small molecules that can bind to these proteins and act as drugs. Proteins in the bHLH-PAS family have to form pairs in order to bind to DNA: NPAS1 and NPAS3 both interact with another bHLH-PAS protein called ARNT, but it is not clear exactly how this works. In 2015, a team of researchers described the shapes that ARNT adopts when it forms pairs with two other bHLH-PAS proteins that are important for sensing when oxygen levels drop in cells. Here, Wu et al. – including many of the researchers involved in the earlier work – have used a technique called X-ray crystallography to determine the three-dimensional shapes of NPAS1 when it is bound to ARNT, and NPAS3 when it is bound to both ARNT and DNA. The experiments show that each of these structures contains four distinct pockets that certain small molecules might be able to bind to. The NPAS1 and NPAS3 structures are similar to each other and to the previously discovered bHLH-PAS structures involved in oxygen sensing. Further analysis of other bHLH-PAS proteins suggests that all the members of this protein family are likely to be able to bind to small molecules and should therefore be considered as potential drug targets. The next step following on from this work is to identify small molecules that bind to bHLH-PAS proteins, which will help to reveal the genes that are regulated by this family. In the future, these small molecules may have the potential to be developed into new drugs to treat psychiatric conditions and other diseases in humans.

Hypoxia is a hallmark of solid tumors that promotes cell growth, survival, and metastasis and confers resistance to chemo and radiotherapies. Hypoxic responses are largely mediated by the transcription factors hypoxia-inducible factor 1α (HIF-1α) and HIF-2α. Our work demonstrates that HIF-2α is essential for colorectal cancer (CRC) progression. However, targeting hypoxic cells is difficult, and tumors rapidly acquire resistance to inhibitors of HIF-2α. To overcome this limitation, we performed a small molecule screen to identify HIF-2α-dependent vulnerabilities. Several known ferroptosis activators and dimethyl fumarate (DMF), a cell-permeable mitochondrial metabolite derivative, led to selective synthetic lethality in HIF-2α-expressing tumor enteroids. Our work demonstrated that HIF-2α integrated 2 independent forms of cell death via regulation of cellular iron and oxidation. First, activation of HIF-2α upregulated lipid and iron regulatory genes in CRC cells and colon tumors in mice and led to a ferroptosis-susceptible cell state. Second, via an iron-dependent, lipid peroxidation-independent pathway, HIF-2α activation potentiated ROS via irreversible cysteine oxidation and enhanced cell death. Inhibition or knockdown of HIF-2α decreased ROS and resistance to oxidative cell death in vitro and in vivo. Our results demonstrated a mechanistic vulnerability in cancer cells that were dependent on HIF-2α that can be leveraged for CRC treatment.

To identify the independent risk factors for placenta accreta spectrum (PAS) and assess the impact of endometrial thickness (EMT) on outcomes after transcervical resection of adhesions (TCRA) for intrauterine adhesions(IUA) prior to in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). This single-center retrospective cohort study included 819 post-TCRA patients between March 2018 and March 2023. Propensity score matching (PSM) was used to balance baseline characteristics. Univariate and multivariate logistic regression analyses identified independent risk factors for PAS. Pregnancy outcomes (biochemical pregnancy, clinical pregnancy, live birth) and adverse obstetric outcomes (PAS, gestational diabetes, preterm delivery, low birth weight) were compared between EMT groups using different cutoffs (6-8 mm). EMT and moderate-to-severe IUA were independent PAS risk factors (severe IUA: aOR=4.998, 95% CI:2.021~12.362). After PSM, the EMT <7 mm group had significantly lower live birth rates (40.3% vs. 55.7%,P=0.005) and higher rates of gestational diabetes,preterm delivery and low birth weight compared to EMT ≥7 mm. Using an 8 mm cutoff, the EMT <8 mm group consistently showed a higher PAS incidence both before (26.4% vs. 13.9%, P=0.001) and after PSM (26.4% vs. 14.7%, P=0.018). In post-TCRA IVF/ICSI-ET patients, EMT and IUA severity are independent PAS risk factors. EMT<7 mm worsens pregnancy outcomes, Exploratory analyses suggested that EMT <8 mm may be associated with higher PAS risk,but this finding requires validation in larger, prospective studies. Given the single-center retrospective design, these results should be interpreted as associative rather than causal. We think optimizing endometrial preparation to achieve a thickness of at least 8 mm may be crucial for reducing PAS and improving reproductive prognosis.

In the last years, the utilization of phytomedicines has increased given their good therapeutic activity and fewer side effects compared to allopathic medicines. However, concerns associated with the biocompatibility and toxicity of natural compounds, limit the phytochemical therapeutic action, opening the opportunity to develop new systems that will be able to effectively deliver these substances. This study has developed a nanocomposite of chitosan (CS) functionalized with graphene oxide (GO) for the delivery of proanthocyanidins (PAs), obtained from a grape seed extract (Ext.). The GO-CS nanocomposite was covalently bonded and was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), atomic force microscopy (AFM) and by dynamic light scattering (DLS). The loading and release of Ext. from the GO-CS nanocomposite were performed in simulated physiological, and the cytotoxicity of the raw materials (GO and Ext.) and nanocomposites (GO-CS and GO-CS-Ext.) was determined using a human kidney cell line (HEK 293). The chemical characterization indicated that the covalent union was successfully achieved between the GO and CS, with 44 wt. % CS in the nanocomposite. The GO-CS nanocomposite was thermostable and presented an average diameter of 480 nm (by DLS). The Ext. loading capacity was approximately 20 wt. %, and under simulated physiological conditions, 28.4 wt.% Ext. (g) was released per g of the nanocomposite. GO-CS-Ext. was noncytotoxic, presenting a 97% survival rate compared with 11% for the raw extract and 48% for the GO-CS nanocomposite at a concentration of 500 µg mL-1 after 24 hrs. Due to π-π stacking and hydrophilic interactions, GO-CS was reasonably efficient in binding Ext., with high loading capacity and Ext. release from the nanocomposite. The GO-CS nanocomposite also increased the biocompatibility of PAs-rich Ext., representing a new platform for the sustained release of phytodrugs.

Increasing the collective contribution of protected areas toward preventing species extinctions requires the strategic allocation of management efforts. Although protected areas (PAs) cover 13% of Earth's land ( 1 ), substantial gaps remain in their coverage of global biodiversity ( 2 ). Thus, there has been emphasis on strategic expansion of the global PA network ( 3 – 5 ). However, because PAs are often understaffed, underfunded, and beleaguered in the face of external threats ( 6 , 7 ), efforts to expand PA coverage should be complemented by appropriate management of existing PAs. Previous calls for enhancing PA management have focused on improving operational effectiveness of each PA [e.g., staffing and budgets ( 6 )]. Little guidance has been offered on how to improve collective effectiveness for meeting global biodiversity conservation goals ( 3 ). We provide guidance for strategically allocating management efforts among and within existing PAs to strengthen their collective contribution toward preventing global species extinctions.

Mining and dams threaten protected areas Over the past two decades, Brazil has emerged as an environmental leader, playing a prominent role in international fora such as the United Nations (UN) Conferences on Sustainable Development. The country has earned praise for the expansion of its protected area (PA) network and reductions in Amazon deforestation. Yet these successes are being compromised by development pressures and shifts in legislation. We highlight concerns for the newly elected government regarding development of major infrastructure and natural resource extraction projects in PAs and indigenous lands (ILs).

In democratic societies, research organizations can offer key policy advice that serves governance and reform practice as part of the larger policy advisory systems (PASs). However, this is rarely the case in authoritarian states, where PASs operate in a distinct way, often with an aim to legitimize the authoritarian rule and ensure regime stability. This case study on the interface between the national government and research organizations that produce policy-relevant research in Kazakhstan demonstrates that researchers working in the authoritarian context often maintain the official state narrative, support regime-friendly policies, and are co-opted by the government through a variety of mechanisms. At the same time, there is space for dissent that is predicated on the financial and ideological independence of private research organizations.

Developing eco-friendly strategies to produce green fuel has attracted continuous and extensive attention. In this study, a novel gas-templating method was developed to prepare 2D porous S-doped g-C3N4 photocatalyst through simultaneous pyrolysis of urea (main g-C3N4 precursor) and ammonium sulfate (sulfur source and structure promoter). Different content of ammonium sulfate was examined to find the optimal synthesis conditions and to investigate the property-governed activity. The physicochemical properties of the obtained photocatalysts were analyzed by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), scanning transmission electron microscopy (STEM), specific surface area (BET) measurement, ultraviolet-visible light diffuse reflectance spectroscopy (UV/vis DRS), X-ray photoelectron spectroscopy (XPS), photoluminescence (PL) spectroscopy and reversed double-beam photo-acoustic spectroscopy (RDB-PAS). The as-prepared S-doped g-C3N4 photocatalysts were applied for photocatalytic H2 evolution under vis irradiation. The condition-dependent activity was probed to achieve the best photocatalytic performance. It was demonstrated that ammonium sulfate played a crucial role to achieve concurrently 2D morphology, controlled nanostructure, and S-doping of g-C3N4 in a one-pot process. The 2D nanoporous S-doped g-C3N4 of crumpled lamellar-like structure with large specific surface area (73.8 m2 g−1) and improved electron−hole separation showed a remarkable H2 generation rate, which was almost one order in magnitude higher than that of pristine g-C3N4. It has been found that though all properties are crucial for the overall photocatalytic performance, efficient doping is probably a key factor for high photocatalytic activity. Moreover, the photocatalysts exhibit significant stability during recycling. Accordingly, a significant potential of S-doped g-C3N4 has been revealed for practical use under natural solar radiation.