Miracle-dz/UniFAR-FTUs huggingface dataset:
Conformational stability of the bacterial adhesin, FimH, with an inactivating mutation

Allostery governing two conformational states is one of the proposed mechanisms for catch‐bond behavior in adhesive proteins. In FimH, a catch‐bond protein expressed by pathogenic bacteria, separation of two domains disrupts inhibition by the pilin domain. Thus, tensile force can induce a conformational change in the lectin domain, from an inactive state to an active state with high affinity. To better understand allosteric inhibition in two‐domain FimH (H2 inactive), we use molecular dynamics simulations to study the lectin domain alone, which has high affinity (HL active), and also the lectin domain stabilized in the low‐affinity conformation by an Arg‐60‐Pro mutation (HL mutant). Because ligand‐binding induces an allostery‐like conformational change in HL mutant, this more experimentally tractable version has been proposed as a “minimal model” for FimH. We find that HL mutant has larger backbone fluctuations than both H2 inactive and HL active, at the binding pocket and allosteric interdomain region. We use an internal coordinate system of dihedral angles to identify protein regions with differences in backbone and side chain dynamics beyond the putative allosteric pathway sites. By characterizing HL mutant dynamics for the first time, we provide additional insight into the transmission of allosteric information across the lectin domain and build upon structural and thermodynamic data in the literature to further support the use of HL mutant as a “minimal model. ” Understanding how to alter protein dynamics to prevent the allosteric conformational change may guide drug development to prevent infection by blocking FimH adhesion.
RDCPF: A Redundancy-Based Duty-Cycling Pipelined-Forwarding MAC for Linear Sensor Networks

Existing duty-cycling and pipelined-forwarding (DCPF) protocols applied in battery-powered wireless sensor networks can significantly alleviate the sleep latency issue and save the energy of networks. However, when a DCPF protocol applies to a linear sensor network (LSN), it lacks the ability to handle the bottleneck issue called the energy-hole problem, which is mainly manifested due to the excessive energy consumption of nodes near the sink node. Without overcoming this issue, the lifespan of the network could be greatly reduced. To that end, this paper proposes a method of deploying redundant nodes in LSN, and a corresponding enhanced DCPF protocol called redundancy-based DCPF (RDCPF) to support the new topology of LSN. In RDCPF, the distribution of energy consumption of the whole network becomes much more even. RDCPF also brings improvements to the network in terms of network survival time, packet delivery latency, and energy efficiency, which have been shown through the extensive simulations in comparison with existing DCPF protocols.
The synergistic proapoptotic effect of PARP-1 and HDAC inhibition in cutaneous T-cell lymphoma is mediated via Blimp-1.

The therapy of advanced mycosis fungoides (MF) presents a therapeutic challenge, and the search for new therapeutic targets is ongoing. Poly(ADP-ribose) polymerase 1 was shown to be upregulated in patients with advanced MF and could be druggable by a new class of chemotherapeutic agents, PARP-1 inhibitors, which are already in clinical trials for other malignancies; however, the role of PARP-1 inhibitors in MF has never been established. We examined the efficacy of talazoparib in the murine model of cutaneous T-cell lymphoma. The cytotoxic effect of talazoparib on Moloney MuLV-induced T-cell lymphoma (MBL2) cells was a result of G2/M cell cycle arrest via the upregulation of p53. The in vivo experiments confirmed the clinical impact of talazoparib on MF tumors. When talazoparib was combined with the histone deacetylase (HDAC) inhibitor, romidepsin, the cytotoxic effect was synergized via downregulation of the DNA-repair genes Fanconianemia complementation group A (FANCA), Fanconi anemia complementation group D2 (FANCD2), and DNA topoisomerase II binding protein 1(TOPBP1)and stimulation of apoptosis via Blimp-1 (PRDM1)/Bax axis. Romidepsin increased the expression of IRF8 and Bcl-6, leading to upregulation of Blimp1and Bax; whereas talazoparib upregulated Blimp-1 and Bax via upregulation of interferon regulatory factor 4 (IRF4), leading to cleavage of caspases 6 and 7. Thus, a combination of talazoparib with romidepsin demonstrated the synergistic antilymphoma effect and warranted further investigation in a clinical trial.
Solid-State NMR and NQR Spectroscopy of Lead-Halide Perovskite Materials

Two- and three-dimensional lead-halide perovskite (LHP) materials are novel semiconductors that have generated broad interest owing to their outstanding optical and electronic properties. Characterization and understanding of their atomic structure and structure–property relationships are often nontrivial as a result of the vast structural and compositional tunability of LHPs as well as the enhanced structure dynamics as compared with oxide perovskites or more conventional semiconductors. Nuclear magnetic resonance (NMR) spectroscopy contributes to this thrust through its unique capability of sampling chemical bonding element-specifically (1/2H, 13C, 14/15N, 35/37Cl, 39K, 79/81Br, 87Rb, 127I, 133Cs, and 207Pb nuclei) and locally and shedding light onto the connectivity, geometry, topology, and dynamics of bonding. NMR can therefore readily observe phase transitions, evaluate phase purity and compositional and structural disorder, and probe molecular dynamics and ionic motion in diverse forms of LHPs, in which they can be used practically, ranging from bulk single crystals (e.g., in gamma and X-ray detectors) to polycrystalline films (e.g., in photovoltaics, photodetectors, and light-emitting diodes) and colloidal nanocrystals (e.g., in liquid crystal displays and future quantum light sources). Herein we also outline the immense practical potential of nuclear quadrupolar resonance (NQR) spectroscopy for characterizing LHPs, owing to the strong quadrupole moments, good sensitivity, and high natural abundance of several halide nuclei (79/81Br and 127I) combined with the enhanced electric field gradients around these nuclei existing in LHPs as well as the instrumental simplicity. Strong quadrupole interactions, on one side, make 79/81Br and 127I NMR rather impractical but turn NQR into a high-resolution probe of the local structure around halide ions.
Binding of SARS‐CoV‐2 to Cell Receptors: A Tale of Molecular Evolution

The magnified infectious power of the SARS‐CoV‐2 virus compared to its precursor SARS‐CoV is intimately linked to an enhanced ability in the mutated virus to find available hydrogen‐bond sites in the host cells. This characteristic is acquired during virus evolution because of the selective pressure exerted at the molecular level. We pinpoint the specific residue (in the virus) to residue (in the cell) contacts during the initial recognition and binding and show that the virus⋅⋅⋅cell interaction is mainly due to an extensive network of hydrogen bonds and to a large surface of noncovalent interactions. In addition to the formal quantum characterization of bonding interactions, computation of absorption spectra for the specific virus⋅⋅⋅cell interacting residues yields significant shifts of Δλmax=47 and 66 nm in the wavelength for maximum absorption in the complex with respect to the isolated host and virus, respectively.
The Termitophilous Scaphidiinae (Coleoptera: Staphylinidae) from Sulawesi, Indonesia

Abstract The three species of termitophilous Scaphidiinae from Sulawesi, Indonesia are reviewed. Vituratella termitophila (Champion, 1927), hitherto known only from continental part of the Oriental region, is newly recorded from Sulawesi. A key to the Sulawesian termitophilous scaphidiines is provided.
Fused Gromov-Wasserstein distance for structured objects: theoretical foundations and mathematical properties

Optimal transport theory has recently found many applications in machine learning thanks to its capacity to meaningfully compare various machine learning objects that are viewed as distributions. The Kantorovitch formulation, leading to the Wasserstein distance, focuses on the features of the elements of the objects, but treats them independently, whereas the Gromov–Wasserstein distance focuses on the relations between the elements, depicting the structure of the object, yet discarding its features. In this paper, we study the Fused Gromov-Wasserstein distance that extends the Wasserstein and Gromov–Wasserstein distances in order to encode simultaneously both the feature and structure information. We provide the mathematical framework for this distance in the continuous setting, prove its metric and interpolation properties, and provide a concentration result for the convergence of finite samples. We also illustrate and interpret its use in various applications, where structured objects are involved.
Non-Vocal Behaviors Are More Frequent During the Decisive Negotiation Phases in Barn Owl Siblings

Simple Summary Animal communication can involve the use of multiple types of signals. While vocal communication has been widely studied in natural populations, there is a dearth of knowledge about the possible role of vibrations or noises made by body movements in communication processes. By using experimental settings both under natural conditions and in the laboratory, we showed that barn owl nestlings (Tyto alba) produced various non-vocal noises. Movement noises were particularly frequent when nestlings were involved in the intense vocal interactions they use to negotiate the priority for access to the next food item delivered by parents. Body movements might therefore have a role in reinforcing vocal signals during competitive interactions among siblings. Abstract Animals produce vibrations or noises by means of body movements, which can play a role in communication. These behaviors enhance signal transmission or receiver attention and could be specifically used during turn-taking phases of a reciprocal exchange of signals. In the barn owl Tyto alba, nestlings vocalize one after the other to negotiate which individual will have priority access to the impending prey item to be delivered by the parents. Owlets adjust their vocalization to their own hunger level and to their siblings’ vocalization, withdrawing from the contest in front of highly vocal, and hence hungry, motivated nestmates. As sibling negotiation is a multicomponent display, we examined whether body movements could also be part of the negotiation process. To this end, we analyzed whether the vocalizations of one nestling affected its nestmate’s movements in three separate experiments: in natural nests, in the lab, and using a playback procedure. Nestling barn owls move in a variety of ways, such as repeated tapping of the floor with a foot, scratching the floor with claws, or flapping wings. Body movements were more frequent during the turn-taking phases of vocal interactions, when siblings emitted longer calls and at a greater rate. Once an individual monopolized vocal activity, siblings became less vocal and less active. Moreover, owlets produced more noisy body movements during the phases of vocal interactions which are crucial to prevail in negotiation. Non-vocal physical activities might reinforce vocal signals during sibling to sibling (sib–sib) interactions, or reflect owlets’ arousal, in the critical period during which they vocally settle which individual will dominate the competition.
Smartphone-Based Whole-Cell Biosensor Platform Utilizing an Immobilization Approach on a Filter Membrane Disk for the Monitoring of Water Toxicants

Bioluminescent bacteria whole-cell biosensors (WCBs) have been widely used in a range of sensing applications in environmental monitoring and medical diagnostics. However, most of them use planktonic bacteria cells that require complicated signal measurement processes and therefore limit the portability of the biosensor device. In this study, a simple and low-cost immobilization method was examined. The bioluminescent bioreporter bacteria was absorbed on a filter membrane disk. Further optimization of the immobilization process was conducted by comparing different surface materials (polyester and parafilm) or by adding glucose and ampicillin. The filter membrane disks with immobilized bacteria cells were stored at −20 °C for three weeks without a compromise in the stability of its biosensing functionality for water toxicants monitoring. Also, the bacterial immobilized disks were integrated with smartphones-based signal detection. Then, they were exposed to water samples with ethanol, chloroform, and H2O2, as common toxicants. The sensitivity of the smartphone-based WCB for the detection of ethanol, chloroform, and H2O2 was 1% (v/v), 0.02% (v/v), and 0.0006% (v/v), respectively. To conclude, this bacterial immobilization approach demonstrated higher sensitivity, portability, and improved storability than the planktonic counterpart. The developed smartphone-based WCB establishes a model for future applications in the detection of environmental water toxicants.
Functional divergence of diacylglycerol acyltransferases in the unicellular green alga Haematococcus pluvialis

Abstract Acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyzes the final committed step in triacylglycerol biosynthesis in eukaryotes. In microalgae, the copy number of DGAT genes is extraordinarily expanded, yet the functions of many DGATs remain largely unknown. This study revealed that microalgal DGAT can function as a lysophosphatidic acyltransferase (LPAAT) both in vitro and in vivo while losing its original function as DGAT. Among the five DGAT-encoding genes identified and cloned from the green microalga Haematococcus pluvialis, four encoded HpDGATs that showed triacylglycerol synthase activities in yeast functional complementation analyses; the exception was one of the type II DGAT encoding genes, HpDGTT2. The hydrophobic recombinant HpDGTT2 protein was purified in soluble form and was found to function as a LPAAT via enzymatic assay. Introducing this gene into the green microalga Chlamydomonas reinhardtii led to retarded cellular growth, enlarged cell size, and enhanced triacylglycerol accumulation, identical to the phenotypes of transgenic strains overexpressing CrLPAAT. This study provides a framework for dissecting uncharacterized DGATs, and could pave the way to decrypting the structure–function relationship of this large group of enzymes that are critical to lipid biosynthesis.
Computational simulation studies on the binding selectivity of Wee1 and Checkpoint kinase 1 by molecular dynamics simulation combined with free energy calculations

Abstract Wee1 kinase and Checkpoint kinase 1 (Chk1) kinase, which are well known to be involved in cancer, are promising targets for cancer therapy. Most of developed Wee1 inhibitors can inhibit activity of Chk1 kinase to different degrees as well. The poor selectivity brought side effects and selective inhibitor is needed. However, the selective mechanisms of Wee1 versus Chk1 are not clear. Therefore, the design of selective Wee1 and Chk1 inhibitors would provide a meaningful starting for the development of anticancer drugs with optimal efficacy. In this study, Wee1 inhibitors with different selectivity over Chk1 were chosen to analyze the selectivity mechanism by means of molecular docking, molecular dynamics simulations and binding free energy calculations. Two key residues of Wee1 kinase and two critical residues of Chk1 were mutated to detect their effect on ligand binding into protein. The results indicated that these residues play a pivotal role in the binding interactions of ligands to receptors through hydrogen bond and hydrophobic interaction with inhibitors. This may provide a better understanding of the selective mechanism of Wee1 and Chk1. It would be beneficial to the discovery and optimization of selective Wee1 and Chk1 inhibitors. Communicated by Ramaswamy H. Sarma
Therapeutic effects of various renin angiotensin modulators on hyperglycemia-induced cataract formation in Sprague Dawley rats

Objects: Our previous research work reported the beneficial effects of angiotensin receptor blockers (ARBs) for the treatment of diabetes associated cataract which was induced by streptozotocin (STZ). The current study, evaluated the effects of topical administration of various renin angiotensin modulators on STZ-induced cataracts in rats. Methods: Single dose of STZ (60 mg/kg, i.p.) was administered in the rats to induce diabetes. Animals were divided into normal and diabetic rats. Normal rats were administered with single dose of sodium citrate buffer (0.1 M, 10ml/kg, i.p.). Diabetic animals were divided into various treatment groups, each group contains six animals and received aliskiren, olmesartan, enalapril, and angiotensin 1–7 at a dose of 0.5% w/v topically on the cornea of the eye for a period of 8 weeks. During experimental protocol morphology of the eyes and lenticular opacity were monitored. Animals were sacrificed after 8 weeks of drug treatment, and various cataractogenic biochemical parameters were assessed. Results: Topical administrations with aliskiren, enalapril, olmesartan, and angiotensin 1–7 showed non-significant alterations in the blood glucose level, but significantly decreased lenticular opacity, restored antioxidant level, restored MDA level and Nitrite content, and decreased the onset of cataract formation. Conclusion: Overall, our findings suggest that topical treatment with renin angiotensin modulators delayed the onset of diabetes-induced cataract formation.
RaveGuard: A Noise Monitoring Platform Using Low-End Microphones and Machine Learning

Urban noise is one of the most serious and underestimated environmental problems. According to the World Health Organization, noise pollution from traffic and other human activities, negatively impact the population health and life quality. Monitoring noise usually requires the use of professional and expensive instruments, called phonometers, able to accurately measure sound pressure levels. In many cases, phonometers are human-operated; therefore, periodic fine-granularity city-wide measurements are expensive. Recent advances in the Internet of Things (IoT) offer a window of opportunities for low-cost autonomous sound pressure meters. Such devices and platforms could enable fine time–space noise measurements throughout a city. Unfortunately, low-cost sound pressure sensors are inaccurate when compared with phonometers, experiencing a high variability in the measurements. In this paper, we present RaveGuard, an unmanned noise monitoring platform that exploits artificial intelligence strategies to improve the accuracy of low-cost devices. RaveGuard was initially deployed together with a professional phonometer for over two months in downtown Bologna, Italy, with the aim of collecting a large amount of precise noise pollution samples. The resulting datasets have been instrumental in designing InspectNoise, a library that can be exploited by IoT platforms, without the need of expensive phonometers, but obtaining a similar precision. In particular, we have applied supervised learning algorithms (adequately trained with our datasets) to reduce the accuracy gap between the professional phonometer and an IoT platform equipped with low-end devices and sensors. Results show that RaveGuard, combined with the InspectNoise library, achieves a 2.24% relative error compared to professional instruments, thus enabling low-cost unmanned city-wide noise monitoring.
Dietary Intake, Mediterranean Diet Adherence and Caloric Intake in Huntington’s Disease: A Review

Decades of research and experimental studies have investigated Huntington’s disease (HD), a rare neurodegenerative disease. Similarly, several studies have investigated whether high/moderate adherence to the Mediterranean Diet and specific macro and micronutrients can decrease cognitive loss and provide a neuroprotective function to neurons. This review systematically identifies and examines studies that have investigated Mediterranean Diet adherence, micro- and macronutrients, supplementation and caloric intake in people with HD, in order to identify if dietary exposures resulted in improvement of disease symptoms, a delay in age of onset or if they contributed to an earlier age of onset in people with HD. A systematic search of PubMed, Directory of open access journal and HubMed was performed independently by two reviewers using specific search terms criteria for studies. The identified abstracts were screened and the studies were included in the review if they satisfied predetermined inclusion criteria. Reference screening of included studies was also performed. A total of 18 studies were included in the review. A few studies found that patients who had high/moderate adherence to Mediterranean Diet showed a slight improvement in their Unified Huntington’s Disease Rating Scale and Total Functional Capacity. In addition, people with HD who had high Mediterranean Diet adherence showed an improvement in both cognitive and motor scores and had a better quality of life compared to patients who had low Mediterranean Diet adherence. Furthermore, a few studies showed that supplementation with specific nutrients, such as triheaptanoin, L-acetyl-carnitine and creatine, had no beneficial effect on the patients’ Unified Huntington’s Disease Rating Scale score. A few studies suggest that the Mediterranean Diet may confer a motor and cognitive benefit to people with HD. Unfortunately, there was little consistency among study findings. It is important for more research to be conducted to have a better understanding of which dietary exposures are beneficial and may result delaying age of onset or disease progression in people with HD.
Genetic polymorphisms among and between blast disease resistant and susceptible finger millet, Eleusine coracana (L.) Gaertn.

Abstract Fungal blast disease is one of the major constraints in finger millet production. Breeding for disease resistance in finger millet, needs characterization of genetic polymorphism among and between the resistant and susceptible genotypes. In total, 67 finger millet genotypes, which are resistant or susceptible to fungal blast disease, were analysed using sequence-related amplified polymorphism (SRAP) and simple sequence repeat (SSR) markers to assess genetic variations and select diverse parents. Twelve each of SRAP and SSR primers produced 95.1 and 93.1% polymorphic bands and grouped them into unweighted pair-group method with arithmetic average clusters. Two of the finger millet genotypes, IE 4709 (blast resistant) and INDAF 7 (susceptible) were distinguished as most diverse genotypes as parents. Several genotype-specific bands observed with SSR primers are potential in developing genotype-specific markers. A high genetic diversity within the resistant and susceptible genotypes, rather than between them, was revealed through Nei's gene diversity (h) index and analysis of molecular variance. The finding helps us to understand the extent of genetic polymorphism between blast disease resistant and susceptible finger millet genotypes to exploit in resistance breeding programs.
Preliminary Attempt to Predict Risk of Invasive Pulmonary Aspergillosis in Patients with Influenza: Decision Trees May Help?

Invasive pulmonary aspergillosis (IPA) is typically considered a disease of immunocompromised patients, but, recently, many cases have been reported in patients without typical risk factors. The aim of our study is to develop a risk predictive model for IPA through machine learning techniques (decision trees) in patients with influenza. We conducted a retrospective observational study analyzing data regarding patients diagnosed with influenza hospitalized at the University Hospital “Umberto I” of Rome during the 2018-2019 season. We collected five IPA cases out of 77 influenza patients. Although the small sample size is a limit, the most vulnerable patients among the influenza-infected population seem to be those with evidence of lymphocytopenia and those that received corticosteroid therapy.