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Background Though compulsive drinking is a hallmark of alcohol use disorder (AUD), little is known of the neural mechanisms driving this behavior. To further the understanding of the neural underpinnings of this compulsivity, a metanalytic approach was used to examine grey matter (GM) volume differences related to AUD, and contrast these differences with GM volume differences in obsessive-compulsive disorder (OCD), to find common underlying regional brain differences. Methods We systematically meta-analyzed case-control studies investigating GM volume that used whole brain voxel-based morphometry separately for AUD and OCD, and then the results of both were directly compared. The Seed-based d Mapping (SDM) software was used to perform the metanalyses. Results The AUD metanalysis used 19 citations, with 736 AUD and 827 control individuals. The OCD metanalysis had 25 citations with 995 OCD and 1177 control individuals. The AUD group showed decreased GM in areas including frontal, limbic, temporal and cerebellar regions. The OCD group had decreased GM in frontal and insular regions but increases in the hypothalamus and brainstem. Importantly, the main outcome showed both groups had decreased GM overlapping in the anterior cingulate and insula. Brain regions were p Conclusions Common brain regional differences in the anterior cingulate and insula that overlap between AUD and OCD suggest that interventions targeting these regions could prove to be beneficial in treating compulsive drinking related to AUD. Further research into the functional role of these brain regions in the etiology of compulsive drinking in AUD is warranted.

Motifs are the evolutionarily conserved patterns which are reported to serve the crucial structural and functional role. Identification of motif patterns in a set of protein sequences has been a prime concern for researchers in computational biology. The discovery of such a protein motif using existing algorithms is purely based on the parameters derived from sequence composition and length. However, the discovery of variable length motif remains a challenging task, as it is not possible to determine the length of a motif in advance. In current work, a k-mer based motif discovery approach called Pr[m], is proposed for the detection of the statistically significant un-gapped motif patterns, with or without wildcard characters. In order to analyze the performance of the proposed approach, a comparative study was performed with MEME and GLAM2, which are two widely used non-discriminative methods for motif discovery. A set of 7,500 test dataset were used to compare the performance of the proposed tool and the ones mentioned above. Pr[m] outperformed the existing methods in terms of predictive quality and performance. The proposed approach is hosted at https://bioserver.iiita.ac.in/Pr[m].

Hepatitis B virus (HBV) middle surface antigen (MHBs) mutation or deletion occurs in patients with chronic HBV infection. However, the functional role of MHBs in HBV infection is still an enigma. Here, we reported that 7.33% (11/150) isolates of CHB patients had MHBs start codon mutations compared with 0.00% (0/146) in acute hepatitis B (AHB) patients. Interestingly, MHBs loss accounted for 11.88% (126/1061) isolates from NCBI GenBank, compared with 0.09% (1/1061) and 0.00% (0/1061) for HBV large surface antigen (LHBs) loss and HBV small surface antigen (SHBs) loss, respectively. One persistent HBV clone of genotype B (B56, MHBs loss) from a CHB patient was hydrodynamically injected into BALB/c mice. B56 persisted for >70 weeks in BALB/c mice, whereas B56 with restored MHBs (B56M+) was quickly cleared within 28 days. Serum cytokine assays demonstrated that CXCL1, CXCL2, IL-6 and IL-33 were significantly increased during rapid HBV clearance in B56M+ mice. Furthermore, the enhancers and promoters of B56 were proved to be required for B56 persistence in mice. Ablating MHBs expression improved the persistence of a new clone (HBV1.3, genotype B) which was recreated by using enhancers and promoters of B56. These data demonstrated that MHBs deletion can promote the persistence of specific HBV variants in a hydrodynamic mouse model. MHBs re-expression restored a rapid clearance of HBV, which was accompanied by cytokine responses including the elevation of CXCL1, CXCL2, IL-6 and IL-33.

Natural product synthesis has been the prime focus for the development of new carbon-carbon bond forming transformations. In particular, the construction of molecules with all-carbon quaternary centers remain one of the most facinating targets. In this regard, transition-metal catalyzed processes have gained imporatnce owing to their mild nature. Towards this, Pd(0)-catalyzed decarboxylative allylations (DcA) is worth mentioning and has emerged as a convenient method for synthesis of molecules even in their enantioenriched form. However, in order to have a flexible approach that facilitate rapid production of derivatives by utilizing commercially available allyl alcohols, the concept of Pd(0)-catalyzed deacylative allylations (DaA) methodology gains popularity. In these reactions, the transfer of an acyl group has a functional role in activating the allylic alcohol (proelectrophile) toward reaction with Pd(0)-catalysts. We present here an Account on newly conceptualized deacylative allylations (DaA) methodology and its applications in the synthesis of various intermediates and building blocks. Further, its potential in the total synthesis of naturally occurring alkaloids have been summarized in this personal account.

The placebo effect, used today as the benchmark to evaluate treatment efficacy, plays a major functional role in traditional medical practices. To better understand its effect at the population level, I use a formal approach to examine the population dynamics of the placebo effect and show a reciprocal causal relationship between belief and efficacy: belief in the efficacy of treatments enhances their realized efficacy, which in turn increases people’s confidence in their therapeutic power. A unique equilibrium for subjective belief and realized efficacy always exists. Its magnitude depends on how beliefs are constructed (relative weight on observed action vs. observed outcome). I further investigate how the placebo effect affects the maintenance of existing medical technologies and the invasion of new technologies by explicitly modeling a belief construction process. Analytical and simulation results show that although the placebo effect primarily suppresses the spread of new technologies, it may occasionally enhance the adoption of superior technological variants under specific parameter combinations.

Curtain fabrics are generally considered as an essential element in the completion of the interior design, which makes the need for it continues. Office curtains play an important role in administrative buildings, as it adds an aesthetical role in addition to its functional role. The research is based on studying the effect of some construction factors on the functional and aesthetical properties of office curtains fabrics, and The research problem is on the lack of methodology for designing and producing office curtains used in administrative buildings in addition to the lack of knowledge of the designers to the properties and nature of chenille yarns and . Typical use of chanilla yarns with restricted and reiterated applied methods. The importance of the research lies in the necessity of giving attention to office curtains and produce new and innovative quality with new aesthetic and weave values of ornamental yarns (Chanelia) for use in administrative buildings. The research aims to Good recruitment of Chanelia yarns to achieve the aesthetic and functional values of the product and production of new office curtain from chanelia yarns that compete with international products. where , in this research , office curtains were produced using fancy yarn, using polyester, acrylic and viscose blended in different ratios. Tests as tensile strength, elongation, air permeability, thickness and weight of fabrics and abrasion resistance were carried out on the samples under study according to the standard conditions required to determine the properties of the product and its suitability for using. The research has reached many results, the most important where sample No. (2) was considered the best sample as it gave the highest value for shrinkage ratio, thickness, weight tensile strength, elongation, , and lowest air permeability . The polyester material has recorded the highest values of tensile strength and air permeability compared to cotton and whereas viscose material has given the lowest of results of tensile strength compared to the other materials, and the acrylic material gave good values for all properties, Obtaining a clear prominence and decline in the curtains produced using the Chanelia yarns, The production of new quality office curtains using chanilla yarns helps to beautify and peculiarity administrative building and the increasing the percentage of fancy yarns, the abrasion resistance, weight, thickness, tensile strength and elongation of the samples become higher .

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, expressed in a variety of cell types and in all tissues, control excitation and rhythm. Since their discovery in neurons and cardiac pacemaker cells, they attracted the attention of medicinal chemistry and pharmacology as novel targets to shape (patho)physiological mechanisms. To date, ivabradine represents the first-in-class drug as specific bradycardic agent in cardiac diseases; however, new applications are emerging in parallel with the demonstration of the involvement of different HCN isoforms in central and peripheral nervous system. Hence, the possibility to target specific isoforms represents an attractive development in this field; indeed, HCN1, HCN2 or HCN4 specific blockers have shown promising features in vitro and in vivo, with remarkable pharmacological differences likely depending on the diverse functional role and tissue distribution. Here, we show a recently developed compound with high potency as HCN2–HCN4 blocker; because of its unique profile, this compound may deserve further investigation.

Sepsis often leads to systemic multiple organ dysfunction, with the majority of deaths attributable to acute myocardial injury (AMI). In this study, we aimed to explore the functional role of miR-365a-3p in sepsis-induced AMI. The sepsis myocardial injury model was constructed using lipopolysaccharide (LPS) both in vitro and in vivo with selective regulation of miR-365a-3p expression. Real-time PCR or Western blot was employed to detect the expressions of miR-365a-3p, inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6), and inflammation-related proteins (nuclear factor-κB (NF-κB), I-κB, myeloid differentiation factor 88 (MyD88)) in myocardial tissues and cells. Also, cell counting kit-8 (CCK8) and flow cytometry assays were used to measure cardiomyocyte proliferation and apoptosis, respectively. Furthermore, the targeting relationship between miR-365a-3p and MyD88 was verified with the dual luciferase activity assay. miR-365a-3p was downregulated in LPS-induced myocardial injury model. miR-365a-3p overexpression attenuated cardiomyocyte apoptosis and suppressed the expressions of inflammatory cytokines and proteins. Inhibiting miR-365a-3p, however, produced the opposite effects. Mechanistically, miR-365a-3p targeted the 3′-untranslated region of MyD88, thereby inactivating MyD88-mediated NF-κB pathway. miR-365a-3p overexpression mitigated sepsis-mediated myocardial injury by inhibiting MyD88-mediated NF-κB activation.

Acetic acid bacteria (AAB) are often considered a threat of the past because today’s equipment allows to perform post-fermentation processes under greatly reduced level of oxygen. This paper deals with the current importance of AAB in brewing. The risk of contamination as well as functional role in spontaneously fermented sour beers is reviewed. The main harmful effect of AAB lies in the direct spoilage of draft beer and formation of biofilms, most often in dispensing systems. On contrary AAB seems to be indispensable in the case of sour beer production. A key issue of AAB in brewing environment is their (early) detection and identification. Therefore, part of this study is devoted to both the latest sophisticated methods and also those of traditional cultivation. which are still prevalent in operating laboratories due to their cost and easy implementation. Finally, the experimental and pictorial material is added as a guide for operations that have less experience with AAB.

Background Brain-resident microglia have a distinct origin compared to macrophages in other organs. Under physiological conditions, microglia are maintained by self-renewal from the local pool, independent of hematopoietic progenitors. Pharmacological depletion of microglia during whole-brain radiotherapy prevents synaptic loss and long-term recognition memory deficits. However, the origin or repopulated cells and the mechanisms behind these protective effects are unknown. Methods CD45low/int/CD11b+ cells from naïve brains, irradiated brains, PLX5622-treated brains and PLX5622 + whole-brain radiotherapy-treated brains were FACS sorted and sequenced for transcriptomic comparisons. Bone marrow chimeras were used to trace the origin and long-term morphology of repopulated cells after PLX5622 and whole-brain radiotherapy. FACS analyses of intrinsic and exotic synaptic compartments were used to measure phagocytic activities of microglia and repopulated cells. In addition, concussive brain injuries were given to PLX5622 and brain-irradiated mice to study the potential protective functions of repopulated cells after PLX5622 + whole-brain radiotherapy. Results After a combination of whole-brain radiotherapy and microglia depletion, repopulated cells are brain-engrafted macrophages that originate from circulating monocytes. Comparisons of transcriptomes reveal that brain-engrafted macrophages have an intermediate phenotype that resembles both monocytes and embryonic microglia. In addition, brain-engrafted macrophages display reduced phagocytic activity for synaptic compartments compared to microglia from normal brains in response to a secondary concussive brain injury. Importantly, replacement of microglia by brain-engrafted macrophages spare mice from whole-brain radiotherapy-induced long-term cognitive deficits, and prevent concussive injury-induced memory loss. Conclusions Brain-engrafted macrophages prevent radiation- and concussion-induced brain injuries and cognitive deficits.

On isolated islands, large arthropods can play an important functional role in ecosystem dynamics. On the Norfolk Islands group, South Pacific, we monitored the diet and foraging activity of an endemic chilopod, the Phillip Island centipede (

Deletion of Phe at position 508 (F508del) in CFTR is the commonest cause of Cystic Fibrosis; this mutation affects the fate of the protein, since most of the F508del-CFTR is retained in the endoplasmic reticulum, ubiquitylated and degraded. CFTR is subjected to different post-translational modifications (PTMs) and the possibility to modulate these PTMs has been suggested as a potential therapeutic strategy for the functional recovery of F508del-CFTR. Recently, it has been suggested the presence of a PTM signature (phosphorylation, methylation and ubiquitylation) in the regulatory insertion element of the CFTR, named PTM-code, which is associated with CFTR maturation and F508del-CFTR recovery. However, the real contribution of these PTMs is still to be deciphered. Here, by using a mutational approach, we show that the PTM-code is dispensable for the functional recovery of F508del-CFTR and therefore its regulation would not be essential in the light of a therapeutical approach.

The use of woven floor covering is not limited to homes only, but it is also used in many public places such as schools, offices, hospitals, restaurants and shops to achieve the aesthetic vision of the place and compatibility with the furniture next to the functional performance. According to the face-to-face technique, two identical carpets are woven at the same time. To obtain this, two superimposed ground fabrics are woven, interlaced by the pile yarns. The fabric so produced is cut in the middle on the weaving machine to obtain two carpets: a bottom and a top carpet. Research problem: The difficulty of producing floor covering with inscriptions and slogans, whether using the flat weaving technique or the pile shape using the Face to Face technology, due to the lack of the first technology for texture and the waste of one carpet in the other. Research objectives: Producing designs characterized by combining different textile methods inside the floor covering and obtaining closed loops and cut on both carpets (top and bottom),Access to an innovative aesthetic product that performs its functional role appropriately and meets the needs of the consumer. Significance: Achieving the possibility of reading the writings in the carpet system face to face as a decorative element to build the design on both carpets (top and bottom) in a terry shape and several levels. (Structural composition). Conclusion : The design of the woven floor covering with the cut and loop technology adds several touches represented in the flat, loop and pile, and also allows reading the artwork on the upper and lower carpet produced ,The possibility of producing two different designs for the upper and lower carpet, Productions of two designs with different design and texture, where one of the two carpets is a loop installation and the other is flat إن إستخدام مفروشات الأرضية ليس قاصرا على المنازل فقط بل أنها تستخدم أيضا فى کثير من الأماکن العامة مثل المدارس والمکاتب والمستشفيات والمطاعم ومحال البيع لتعمل على تحقيق الرؤية الجمالية للمکان والتوافق مع الأثاث بجوار الاداء الوظيفى، وکلمة معلق لفظا وتوظيفا مصطلح يستخدم عند تناول لوحة فنية منسوجة. ولقد جذب الحرف العربى انتباه الفنانين الغربيين ،سواء بسبب بنيته الفنية الجمالية او بسبب التزيينات التجريدية التى کانت ترافقه، وعلى ذلک فقد استعمل بعض الفنانين الغربين مثل :بول کلى ونالارد وديجوتکس وتروکس وهوفر وسينجيه الحرف العربى کماهو مألوف فى الفن العربى ،واستوحى فنانون اخرون ذلک ولکن باستعمال الحرف اللاتينى او العدد امثال :جوسبر جونز. ويضيف إنتاج مفروشات الارضية بطريقة Face to Faceو بتقنية ال cut and loop ملامس عدة ممثلة فى flat weave ,loop ,pile کما يتيح قراءة العمل الفنى بالسجادة العلوية والسفلية المنتجة فى آن واحد . مشکلة البحث : صعوبة إنتاج مفروشات الأرضية بتقنية Face to Face ذات الکتابات والشعارات کما بشکل3 لاهدار احدى السجادتين، وافتقارتقنية ال Flat weaving شکل 4 فى عمل ملامس مختلفة بتصميم الکتابات . اهداف البحث: انتاج تصميمات تتميز بالدمج بين أساليب نسجية مختلفة داخل مفروشات الارضية و الحصول على عراوي مقفولة و مقصوصة بوجه واحد من المنسوج و الوصول إلى منتج جمالى مبتکر يؤدى دوره الوظيفى بشکل مناسب ويلبى إحتياجات المستهلک.. منهجية البحث : يتبع البحث المنهج التجريبي التحليلي. نتائج البحث: تمکنت الدراسة من تحقيق إمکانيه قراءة الکتابات فى السجاد المنسوج بطريقة وجها لوجه کعنصر زخرفى لبناء التصميم بکلا السجادتين (الوجه والظهر) بشکل وبرى ومستويات عدة .(الترکيب البنائى)

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. We demonstrated that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine, musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell (hiPSC)-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that exhibit liver enrichment. Treatment with GalNAc-HULC mimics reduced excessive phenylalanine in Pair(−/−) and Pah(R408W/R408W) mice and improved the phenylalanine tolerance of these mice.

Melanin-based plumage coloration in birds is determined by the ratio and distribution in the feathers of two types of melanin pigments, eumelanin and pheomelanin. The review focuses on different aspects of melanogenesis and transport and deposition of melanins, as well as on gene regulation of numerous processes associated with them. Modern concepts on the functional role of candidate genes are presented and the results of the analysis of their variability in representatives of different bird species are described. The data on the use of whole genome and transcriptome analyses to study the molecular genetic bases of the plumage coloration and pattern are presented.

Las emociones positivas son valoradas y buscadas en nuestra vida diaria, pero aún no se comprende bien el rol funcional que juegan en la cognición humana. A pesar de ciertas similitudes, las emociones positivas y negativas parecen depender de vías neuronales distintas y, por tanto, podrían influir de manera diferente en funciones cognitivas como la memoria. En este artículo de revisión, se presentan los efectos cognitivos y los fundamentos neuronales de las emociones positivas, centrándose en las especificidades de las emociones inducidas por el humor. Posteriormente, se describe la influencia beneficiosa del humor sobre la memoria y se analizan los posibles mecanismos neuronales a través de los cuales el humor puede mejorar la memoria en el cerebro humano., As emoções positivas são valorizadas e procuradas em nossa vida diária, mas seu papel funcional na cognição ainda é pouco compreendido. Apesar de certas semelhanças, as emoções positivas e negativas dependem de vias neuronais distintas e podem, portanto, influenciar de forma diferente as funções cognitivas, como a memória. Neste artigo de revisão, apresento primeiro os efeitos cognitivos e as bases neurais das emoções positivas, focalizando as especificidades das emoções induzidas por humor. Posteriormente, descrevo a influência benéfica do humor na memória e discuto os possíveis mecanismos neurais que podem melhorar a memória relacionada ao humor no cérebro humano., Positive emotions are valued and sought after in our daily lives, but their functional role in cognition is still poorly understood. Despite common ground, positive and negative emotions would rely on distinct neuronal pathways and might therefore differently influence cognitive functions such as memory. In this review, I first present the cognitive effects and neural underpinnings of positive emotions, focusing on the specificities of humor-induced emotions. Second, I describe the beneficial influence of humor on memory, and I discuss potential neural mechanisms that can support humor-related memory improvement in the human brain., Dossier: Memoria y emoción, Facultad de Psicología

Ribosome stalling during translation significantly reduces cell viability, because cells have to spend resources on the synthesis of new ribosomes. Therefore, all bacteria have developed various mechanisms of ribosome rescue. Usually, the release of ribosomes is preceded by hydrolysis of the tRNApeptide bond, but, in some cases, the ribosome can continue translation thanks to the activity of certain factors. This review describes the mechanisms of ribosome rescue thanks to trans-translation and the activity of the ArfA, ArfB, BrfA, ArfT, HflX, and RqcP/H factors, as well as continuation of translation via the action of EF-P, EF-4, and EttA. Despite the ability of some systems to duplicate each other, most of them have their unique functional role, related to the quality control of bacterial translation in certain abnormalities caused by mutations, stress cultivation conditions, or antibiotics.

Nanoparticle size plays a central role in determining material properties and performance in biomedical applications. A wide variety of functional nanomaterials and nano-bioconjugates have been developed for monitoring biochemical activity, controlling biological functions, and therapeutic applications. This review focuses on the role of nanoparticle size (typically in the range of 1–100 nm) in various biomedical applications, the origin of such a size effect, and the optimum size requirement for the best performance in different biomedical applications. First, we discuss various nanoscale units present in life processes along with their size and functional role. Next, we discuss the size-dependent properties of some well-known nanoparticles and how those properties are exploited in different biomedical applications. Next, we discuss the size-dependent performance of functional nanomaterials and nano-bioconjugates that are used in various biomedical applications. Then, we highlight some of the best designed nanoparticles of optimum size for specific biomedical applications. Finally, we attempt to correlate the origin of the evolutionary selection of various nanoscale units in life processes toward specific biological functions.

In recent work, Sarah Robins, Gerardo Viera and Steven James have provided some insightful objections to the ideas offered in my book, Memory: A Self-Referential Account. In this paper, I put forward some responses to those objections. Robins challenges the idea that being a memory could be a matter of having a particular functional role within the subject’s cognitive economy. Viera challenges the idea that the content of a memory could explain some of its phenomenological properties. And James challenges the idea that our memories could be immune to error through misidentification. All three commentators are targeting, not tangential aspects of, but fundamental assumptions in the account of memory proposed in the book. For that reason, modifying some of those assumptions would amount to proposing a whole different account of memory. I hope to show, however, that such a radical move is not necessary. For there are possible responses to the objections from all three commentators which are available within the constraints of the account proposed in the book.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases known to degrade extracellular matrix (ECM). Being involved in many biological and physiological processes of tissue remodeling, MMPs play a crucial role in many pathological conditions such as arthritis, cancer, cardiovascular diseases, etc. Typically, MMPs possess a propeptide, a zinc-containing catalytic domain, a hinge region and a hemopexin domain. Based on their structural domain organization and substrates, MMPs are classified into six different classes, viz. collagenases, stromelysins, gelatinases, matrilysins, membrane-type and other MMPs. As per previous studies, a set of invariant water (IW) molecules of MMP-1 (a collagenase) play a significant role in stabilizing their catalytic domain. However, a functional role of IW molecule in other classes of MMPs has not been reported yet. Thus, in this study, IW molecules of MMPs from different classes were located and their plausible role(s) have been assigned. The results suggest that IW molecules anchor the structurally and functionally essential metal ions present in the vicinity of the active site of MMPs. Further, they (in)directly interlink different structural features and bridge the active site metal ions of MMPs. This study provides the key IW molecules that are structurally and functionally relevant to MMPs and hence, in turn, might facilitate the development of potent generalized inhibitor(s) against different classes of MMPs. Communicated by Ramaswamy H. Sarma.

Noailles burins are one of the main lithic types of the European Upper Palaeolithic which characterizes the “Noaillian” Gravettian. Their typological definition is well accepted today by the scientific community despite a long debate lasted several decades between the nineteenth and twentieth centuries. On the contrary, the functional role of Noailles burins remains a matter of debate. In order to provide new evidence about the interpretation of the Noailles burins, this paper combines techno-typological and functional data. At this regard, the entire collection of Noailles burins found in the east sector of the well-known site of Riparo Mochi (Balzi Rossi, Italy) has been studied. Our data, also compared with the European scenario, allow to reconsider the significance of the Noailles burins within the economy of the Noaillian hunter-gatherers.

Action-stopping in humans involves bursts of beta oscillations in prefrontal-basal ganglia regions. To determine the functional role of these beta bursts we took advantage of the Race Model framework describing action-stopping. We incorporated beta bursts in three race model variants, each implementing a different functional contribution of beta to action-stopping. In these variants, we hypothesized that a transient increase in beta could 1) modulate decision thresholds, 2) change stop accumulation rates, or 3) promote the interaction between the Stop and the Go process. We then tested the model predictions using EEG recordings in humans performing a Stop-signal task. We found that the model variant in which beta increased decision thresholds for a brief period of time best explained the empirical data. The model parameters fitted to the empirical data indicated that beta bursts involve a stronger decision threshold modulation for the Go process than for the Stop process. This suggests that prefrontal beta influences stopping by temporarily holding the response from execution. Our study further suggests that human action-stopping could be multi-staged with the beta acting as a pause, increasing the response threshold for the Stop process to modulate behavior successfully. Our novel approach of introducing transient oscillations into the race model and testing against human neurophysiological data allowed us to discover potential mechanisms of prefrontal beta, possibly generalizing its role in situations requiring executive control over actions.

The article is devoted to the problem of the functional role of imagination in the processes of conscious self-regulation of personality as a complex integrative phenomenon. The need to consider conscious self-regulation in the context of the resource approach is determined. Conscious self-regulation, manifesting itself in the initiative-creative mode, in the ease and success of mastering new types of purposeful activity, in the ability to solve non-standard tasks, in changing conditions that require changes, etc., associated with the generalized ability to set goals, to model significant external and internal conditions, to program actions, to control and evaluate current and final results, and to adjust the regulatory system. The adequacy of these skills to the requirements of the activity, their flexibility and reliability is largely determined by the functional involvement of the imagination in self-regulatory processes, where it 1) provides goal setting (goal-setting function) and expanding activity’s meaning basis (meaning-making function); 2) participates in modeling and subsequent productive transformation of the figurative content of the problem situation (modeling function); 3) enables reflexive regulation (control, evaluation, correction) by a person of his/her own actions and deeds, which determines the constructive direction of activity (reflexive-regulatory function)., Стаття присвячена проблемі функціональної ролі уяви в процесах свідомої саморегуляції особистості як складного інтегративного феномену. Визначається необхідність розглядати усвідомлену саморегуляцію у контексті ресурсного підходу. Описуються цілеутворювальна, смислоутворювальна, моделююча та рефлексивно-регуляторна функції уяви та розкривається їхній зв’язок з процесами усвідомленої саморегуляції.

Attention-dependent reduction in the tendency for neurons to fire bursts (burstiness) is widely observed in the visual cortex. However, the underlying mechanism and the functional role of this phenomenon remain unclear. We recorded well-isolated single-unit activities in primary visual cortex (V1) from two primates (Macaca mulatta) while they performed a detection task engaging spatial attention with two levels of difficulty (hard/easy). We found that attention modulated burstiness of V1 neurons in a cell-type specific manner. For neurons whose net response enhanced with the increase of task difficulty (difficulty-enhanced neuron), representing their involvement in boosting the signal of the attended stimulus, attention led to a reduction in burstiness during hard task but not during easy task. In contrast, regardless of the level of task difficulty, attention-dependent reduction in burstiness was not observed in neurons that showed a net suppression in firing rate with the increase of task difficulty (difficulty-suppressed neuron), indicating their commitment in filtering out the interference of distractor. This differentiation in the effects of attentional modulation on burstiness among the cells with distinct functional roles in attention suggests that the reduction in burstiness by attention is linked to target enhancement and is not associated with distractor suppression.

As the largest organ in our body, the skin acts as a barrier against external stress and damages. There are various cell types of skin, such as keratinocytes, melanocytes, fibroblasts, and skin stem cells. Korean ginseng, which is one of the biggest distributions of ginseng worldwide, is processed into different products, such as functional food, cosmetics, and medical supplies. This review aims to introduce the functional role of Korean ginseng on different dermal cell types, including the impact of Korean ginseng in anti-photodamaging, anti-inflammatory, anti-oxidative, anti-melanogenic, and wound healing activities, etc. We propose that this information could form the basis of future research of ginseng-derived components in skin health.

Background Food colloid stability is critical to many food properties and surfactants that can provide long-term stability against phase separation are highly desirable. The hydrophobins and the chaplins are proteins secreted by filamentous microorganisms that spontaneously self-assemble into amphipathic layers at a hydrophilic-hydrophobic interface providing surface activity. These proteins have great potential as biosurfactants or foaming agents in food products and other dispersed systems. Scope and approach This review seeks to provide a better understanding of the common structural features of the hydrophobin and chaplin proteins and their functional properties, including surface activity, which arise from these structural features. The ability of these two protein classes to assemble at the interface and stabilize dispersed systems is compared. The mechanism of protein self-assembly at the interface, role of cysteine residues in self-assembly and the formation of fibrils are also explored. Potential methods and challenges in the production of these proteins for commercial applications are reviewed, together with new promising areas of research. Key findings and conclusions The hydrophobins and chaplins display a surface activity comparable to traditional surfactants and form interfacial films with highly favourable rheological properties. Proteins from these two groups of naturally derived molecules have the potential to stabilize food or pharmaceutical dispersions against coalescence and disproportionation over a wide range of pH for lengthy periods of time (up to 45 days). While there is a significant promise for their use in the stabilization of dispersed systems, further optimization of protein production yield will be required for commercial applications.

OBJECTIVE: Spinal cord injury (SCI) is a severe traumatic disease in the central nervous system, and can result in neuronal injury. Altered miRNA expression is identified to be involved in the pathogenesis of SCI. DESIGN: This study investigated the clinical value of miR-142-5p in SCI patients, and explored its functional role in the regulation of inflammatory. SETTING: The First Affiliated Hospital of Soochow University. PARTICIPANTS: Ninety-eight patients with acute spinal trauma. INTERVENTIONS: All patients were recruited, and divided into complete SCI group, incomplete SCI group and normal nerve function group. OUTCOME MEASURES: Real-time quantitative PCR (qRT-PCR) was used to detect the expression levels of miR-142-5p. CCK-8 and flow cytometry assay were performed to evaluate the cell viability and apoptosis. ELISA assay was applied to estimate the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). RESULTS: Serum miR-142-5p level was significantly increased in SCI patients, especially the complete SCI cases. ROC curve analysis suggested miR-142-5p could distinguish SCI patients from normal nerve function patients and was associated with the severity of SCI. A positive association was detected between miR-142-5p and serum levels of IL-6, TNF-α in SCI patients. Downregulation of miR-142-5p significantly reduced the protein levels of both IL-6 and TNF-α in LPS treated PC12 cells, and weakened LPS induced cell apoptosis. CONCLUSION: MiR-142-5p is a potential biomarker for the occurrence of SCI in acute spinal trauma patients. Downregulation of miR-142-5p plays an anti-inflammatory effect for SCI patients.

Neuropeptides are an important class of endogenous peptides in the nervous system that regulate physiological functions such as feeding, glucose homeostasis, pain, memory, reproduction, and many others. In order to understand the functional role of neuropeptides in diseases or disorders, studies investigating their dysregulation in terms of changes in abundance and localization must be carried out. As multiple neuropeptides are believed to play a functional role in each physiological process, techniques capable of global profiling multiple neuropeptides simultaneously are desired. Mass spectrometry is well-suited for this goal due to its ability to perform untargeted measurements without prior comprehensive knowledge of the analytes of interest. Mass spectrometry imaging (MSI) is particularly useful because it has the capability to image a large variety of peptides in a single experiment without labeling. Like all analytical techniques, careful sample preparation is critical to successful MSI analysis. The first half of this review focuses on recent developments in MSI sample preparation and instrumentation for analyzing neuropeptides and other biomolecules in which the sample preparation technique may be directly applicable for neuropeptide analysis. The benefit offered by incorporating these techniques is shown as improvement in a number of observable neuropeptides, enhanced signal to noise, increased spatial resolution, or a combination of these aspects. The second half of this review focuses on recent biological discoveries about neuropeptides resulting from these improvements in MSI analysis. The recent progress in neuropeptide detection and analysis methods, including the incorporation of various tissue washes, matrices, instruments, ionization sources, and computation approaches combined with the advancements in understanding neuropeptide function in a variety of model organisms, indicates the potential for the utilization of MSI analysis of neuropeptides in clinical settings.

Protein changes under drought or water stress conditions have been widely investigated. These investigations have given us enormous understanding of how drought is manifested in plants and how plants respond and adopt to such conditions. Chlorophyll fluoroescence, gas exchange, OMICS, biochemical and molecular analyses have shed light on regulation of physiology and photosynthesis of plants under drought. Use of proteomics has greatly increased the repertoire of drought-associated proteins which nevertheless, need to be investigated for their mechanistic and functional roles. Roles of such proteins have been succinctly discussed in various review articles, however more information on their functional role in countering drought is needed. In this review, recent developments in the field, alterations in the abundance of plant proteins in response to drought, monitored through numerous proteomic and immuno-blot analyses, and how these could affect plants growth and development, are discussed.

Recent investigations in bacteria suggest that membraneless organelles play a crucial role in the subcellular organization of bacterial cells. However, the biochemical functions and assembly mechanisms of these compartments have not yet been completely characterized. This Review assesses the current methodologies used in the study of membraneless organelles in bacteria, highlights the limitations in determining the phase of complexes in cells that are typically an order of magnitude smaller than a eukaryotic cell, and identifies gaps in our current knowledge about the functional role of membraneless organelles in bacteria. Liquid-liquid phase separation (LLPS) is one proposed mechanism for membraneless organelle assembly. Overall, we outline the framework to evaluate LLPSin vivoin bacteria, we describe the bacterial systems with proposed LLPS activity, and we comment on the general role LLPS plays in bacteria and how it may regulate cellular function. Lastly, we provide an outlook for super-resolution microscopy and single-molecule tracking as tools to assess condensates in bacteria.Statement of SignificanceThough membraneless organelles appear to play a crucial role in the subcellular organization and regulation of bacterial cells, the biochemical functions and assembly mechanisms of these compartments have not yet been completely characterized. Furthermore, liquid-liquid phase separation (LLPS) is one proposed mechanism for membraneless organelle assembly, but it is difficult to determine subcellular phases in tiny bacterial cells. Thus, we outline the framework to evaluate LLPSin vivoin bacteria and we describe the bacterial systems with proposed LLPS activity in the context of these criteria.

In article the essence and the maintenance of the salary as economic category, one of the main directions of increase in profi tability of work of employees of agricultural branch in modern economic conditions is considered. The economic analysis and assessment of realization of her main functions in the organization of compensation of hired employees of the organizations are given, a number of the directions of their development for the purpose of strengthening of motivation of workers in results of the work is off ered.

Background Rhinoplasty and rhinoseptoplasty are very common and complex surgical procedures whereas the nose plays an important functional role in breathing and an aesthetic role in the mid face. Methods Modified Heidemann spatula is characterized by a hand piece and two faces in the end of the instrument, both of them blunt and each one with a different slant; we have modified the ends of the instrument edging them. Results The advantages of modified Heidemann spatula are the easy detachment of the mucosa and the submucosal septal up to the thin caudal perichondrium starting from the columellar region, easily identifying the cleavage plane and then practicing the perichondral dissection of the septum bilaterally without damaging the mucosa. Conclusion The modified Heidemann spatula, with its two cutting parts, becomes a very valid surgical instrument in septoplasty and rhinoseptoplasty surgery, providing multiple advantages.

Human milk is elixir for neonates and is a rich source of nutrients and beneficial microbiota required for infant growth and development. Its benefits prompted research into probing the milk components and their use as prophylactic or therapeutic agents. Culture-independent estimation of milk microbiome and high-resolution identification of milk components provide information, but a holistic purview of these research domains is lacking. Here, we review the current research on bio-therapeutic components of milk and simplified future directions for its efficient usage. Publicly available databases such as PubMed and Google scholar were searched for keywords such as probiotics and prebiotics related to human milk, microbiome and milk oligosaccharides. This was further manually curated for inclusion and exclusion criteria relevant to human milk and clinical efficacy. The literature was classified into subgroups and then discussed in detail to facilitate understanding. Although milk research is still in infancy, it is clear that human milk has many functions including protection of infants by passive immunization through secreted antibodies, and transfer of immune regulators, cytokines and bioactive peptides. Unbiased estimates show that the human milk carries a complex community of microbiota which serves as the initial inoculum for establishment of infant gut. Our search effectively screened for evidence that shows that milk also harbours many types of prebiotics such as human milk oligosaccharides which encourage growth of beneficial probiotics. The milk also trains the naive immune system of the infant by supplying immune cells and stimulatory factors, thereby strengthening mucosal and systemic immune system. Our systematic review would improve understanding of human milk and the inherent complexity and diversity of human milk. The interrelated functional role of human milk components especially the oligosaccharides and microbiome has been discussed which plays important role in human health.

In budding yeast, Rif1 negatively regulates telomere length, but the mechanism of this regulation has remained elusive. Previous work identified several functional domains of Rif1, but none of these has been shown to mediate telomere length. To define Rif1 domains responsible for telomere regulation, we localized truncations of Rif1 to a single specific telomere and measured telomere length of that telomere compared to bulk telomeres. We found that a domain in the N-terminus containing HEAT repeats, Rif1177–996, was sufficient for length regulation when tethered to the telomere. Charged residues in this region were previously proposed to mediate DNA binding. We found that mutation of these residues disrupted telomere length regulation even when Rif1 was tethered to the telomere. Mutation of other conserved residues in this region, which were not predicted to interact with DNA, also disrupted telomere length maintenance, while mutation of conserved residues distal to this region did not. Our data suggest that conserved amino acids in the region from 436 to 577 play a functional role in telomere length regulation, which is separate from their proposed DNA binding function. We propose that the Rif1 HEAT repeats region represents a protein-protein binding interface that mediates telomere length regulation.

The article deals with both juxtaposition and differentiation of the concepts of “basic principles” and jus cogens (peremptory norms of general international law) as phenomena of international legal reality from the point of view of their location in the theory and practice of international law. Not limited to fixing a serious problem that exists in the field of research and consists in a considerable variety of terms having complicated the apparatus of modern international legal science, this article provides a consistent differentiation of many other individual notions which fall under the head of the principles of international law. Along with this, as the key-stone of the problem under consideration the broader “layer” — the analysis of the “principle” as a category of legal science shall be subject to accentuation as core, dominant in modern international law. Since the “basic principles” are one of the main concepts of both the system of international law and its science, they are evaluated primarily from the point of view of their functional role in the legal regulation of interstate relationships. While being compared with the peremptory norms of general international law (jus cogens), the basic principles are also envisaged in this article aiming to determine their importance for the theory and practice of international law in general.

In the Arctic ecosystems, fungi are crucial for interactions between soil and plants, the cycling of nutrients, and the transport of carbon. To date, no studies have been conducted to thoroughly examine the mycobiome and its functional role in various habitats of the High Arctic region. The aim was to unravel the mycobiome in the nine habitats (i.e., soil, lichen, vascular plant, moss, freshwater, seawater, marine sediment, dung, and marine alga) in the Ny-Ålesund Region (Svalbard, High Arctic) using a high-throughput sequencing approach. A total of 10,419 ASVs were detected. Among them, 7535 ASVs were assigned to unidentified phyla, while the remaining 2884 ASVs were assigned to 11 phyla, 33 classes, 81 orders, 151 families, 278 genera, and 261 species that were known. The distribution of the mycobiome was driven by habitat specificity, indicating that habitat filtering is a crucial factor influencing the fungal assemblages at a local scale in this High Arctic region. Six growth forms and 19 fungal guilds were found. The ecological guild (e.g., lichenized, ectomycorrhizal) and growth form (e.g., yeast, thallus photosynthetic) varied significantly among various habitats. In addition, the occurrence of 31 fungal species that are considered to be potential pathogens was determined. These results will increase our understanding of fungal diversity and its functional significance in this distinctive High Arctic area and thereby establish the groundwork for prediction about how the mycobiome will alter in various environments as a result of anticipated climate change.

Reduced protein levels of SMARCB1 (a.k.a. BAF47, INI1, SNF5) have long been observed in synovial sarcoma (SS). Here, we show that combined Smarcb1 genetic loss with SS18-SSX expression in mice synergized to produce aggressive tumors with histomorphology, transcriptomes, and genome-wide BAF-family complex distributions distinct from SS18-SSX alone, indicating a defining role for SMARCB1 in SS. Smarcb1 silencing alone in mesenchyme modeled epithelioid sarcomagenesis. In mouse and human SS cells, SMARCB1 was identified within PBAF and canonical BAF (CBAF) complexes, co-incorporated with SS18-SSX in the latter. Recombinant expression of CBAF components in human cells reconstituted CBAF sub-complexes that contained equal levels of SMARCB1, regardless of SS18 or SS18-SSX inclusion. In vivo, SS18-SSX expression led to whole-complex CBAF degradation, rendering increases in the relative prevalence of other BAF-family subtypes, PBAF and GBAF complexes, over time. Thus, SS18-SSX alters BAF subtypes levels/balance and genome distribution, driving synovial sarcomagenesis.

We studied the metabolic phenotype of a novel Ucp1-LUC-iRFP713 knock-in reporter gene mouse model originally generated to monitor endogenous Ucp1 gene expression. Both reporter mice and reporter cells reliably reflected Ucp1 gene expression in vivo and in vitro. We here report an unexpected reduction in UCP1 content in homozygous knock-in (KI) reporter mice. As a result, the thermogenic capacity of KI mice stimulated by norepinephrine was largely blunted, making them more sensitive to an acute cold exposure. In return, these reporter mice with reduced UCP1 expression enabled us to investigate the physiological role of UCP1 in the prevention of weight gain. We observed no substantial differences in body mass across the three genotypes, irrespective of the type of diet or the ambient temperature, possibly due to the insufficient UCP1 activation. Indeed, activation of UCP1 by daily injection of the selective β(3)-adrenergic receptor agonist CL316,243 resulted in significantly greater reduction of body weight in wild-type mice than in KI mice. Taken together, we conclude that the intact expression of UCP1 is essential for cold-induced thermogenesis but the presence of UCP1 per se does not protect mice from diet-induced obesity. NEW & NOTEWORTHY To study the functional role of UCP1-dependent brown adipose tissue thermogenesis for energy balance, new animal models are needed. By metabolic phenotyping of a novel mouse model with low UCP1 levels in brown fat, we demonstrate that the susceptibility to diet-induced obesity is not increased despite impaired cold-induced thermogenic capacity. Brown fat requires pharmacological activation to promote negative energy balance in diet-induced obese mice.

Rapid eye movements (REM) during sleep is a descriptor of the REM sleep stage. Parameters associated with REM sleep, such as REM sleep numbers, REM density, REM latency, and pre-REM negativity have been associated with the functional role of REM sleep. The temporal properties of these parameters appear to play an essential role in REM sleep, so precise knowledge of these temporal properties, particularly REM onset, can help elucidate the temporal dynamics of neural activity related to REM sleep. However, manual detection of this event is a time-consuming and subjective process that can be facilitated by an automatic detection tool. We developed an automatic REM onset detection algorithm based on features describing rapid eye movements and compared the results obtained with human detection by a sleep expert.

Histone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.