Explore the vast range of titles available.

Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.

California is the world’s biggest producer and exporter of almonds. Currently, the sweeping of almonds during the harvest creates a significant amount of dust, causing air pollution in the neighboring urban areas. A low-dust sweeping system was designed to reduce the dust during the sweeping of almonds in the orchard. The system includes a feedback control system to control the sweeper brushes’ height and their angular velocity by adjusting the forward velocity of the harvester and the brushes’ rotational speeds to avoid any extra overlapping sweeping, which increases dust generation. The governing kinematic equations for sweepers’ angular velocity and vehicle forward speed were derived. The feedback controllers for synchronizing these speeds were designed to optimize brush/dust contact to minimize dust generation. The sweepers’ height controller was also designed to stabilize the gap between the brushes and the orchard floor and track the road trajectory. Controllers were simulated and tuned for a fast response for agricultural applications with less than a second response delay. Results showed that the designed system has acceptable performance and generates low amounts of dust within the acceptable range of California ambient air quality standards.

Background The Hippo pathway functions as a tumor suppressor pathway in human cancers, while dysfunction of the Hippo pathway is frequently observed in malignancies. Although YAP/TAZ activity is tightly controlled by the phosphorylation cascade of the MST-LATS-YAP/TAZ axis, it is still unclear why the YAP/TAZ proteins are activated in human cancers despite Hippo pathway activation. Recent studies have suggested that in addition to phosphorylation, several other posttranslational modifications, including ubiquitination, also play critical roles in modulating TAZ function. Methods We used several gastric cancer cell lines and performed western blot analysis, real-time PCR, immunoprecipitation assays, and in vitro ubiquitination assays and established a xenograft mouse model. Results Here, by screening a DUB (deubiquitinase) siRNA library, we discovered that DUB1 functions as a critical modulator that facilitates gastric cancer stemness and progression by deubiquitinating and activating the TAZ protein. We also found that DUB1 expression was elevated in gastric cancer and that elevated DUB1 expression correlated with TAZ activation and poor survival. DUB1 associates with the TAZ protein and deubiquitinates TAZ at several lysine residues, which subsequently stabilizes TAZ and facilitates its function. Conclusions Our study revealed a novel deubiquitinase in the Hippo/TAZ axis and identified one possible therapeutic target for Hippo-driven gastric cancer. Highlights 1. DUB1 is an important modulator of Hippo signaling in gastric cancer. 2. DUB1 expression is elevated in human gastric cancer samples and correlates with poor survival in gastric cancer. 3. DUB1 facilitates gastric cancer progression via the Hippo/TAZ axis. 4. DUB1 associates with TAZ and directly inhibits YAP polyubiquitination and degradation.

Breast cancer is one of the most common malignancies worldwide, while the luminal types (ERα positive) accounts for two third of all breast cancer cases. Although ERα positive breast cancer could be effective controlled by endocrine therapy, most of the patients will develop endocrine resistance, which becomes a headache clinical issue for breast cancer field. Endocrine resistance could be caused by multiple pathway disorders, the dys-regulation of ERα signaling might be a critical factor, which makes it urgent and important to reveal the potential molecular mechanism of ERα signaling. In our current study, we identified a new deubiquitination enzyme USP1 through screening the whole DUB (Deubiquitinases) siRNA library. The expression of USP1 is elevated in human breast cancer compared with normal mammary tissues. Importantly, USP1 expression levels are specially correlated with poor survival in ERα positive patients. USP1 depletion inhibited breast cancer cell progression and ERα signaling activity. Immuno-precipitation assays indicate that USP1 associates with ERα and promotes its stability possibly via inhibiting ERα K48-linked poly-ubiquitination. In conclusion, our data implicate a non-genomic mechanism by USP1 via stabilizing ERα protein controls ERα target gene expression linked to breast cancer progression.

In this article, we look at the stochastic Wu–Zhang system (SWZS) forced by multiplicative Brownian motion in the Itô sense. The mapping method, which is an effective analytical method, is employed to investigate the exact wave solutions of the aforementioned equation. The proposed scheme provides new types of exact solutions including periodic solitons, kink solitons, singular solitons and so on, to describe the wave propagation in quantum mechanics and analyze a wide range of essential physical phenomena. In the absence of noise, we obtain some previously found solutions of SWZS. Additionally, using the MATLAB program, the impacts of the noise term on the analytical solution of the SWZS were demonstrated.

Acute respiratory distress syndrome (ARDS) is associated with a heterogeneous pattern of injury throughout the lung parenchyma that alters regional alveolar opening and collapse time constants. Such heterogeneity leads to atelectasis and repetitive alveolar collapse and expansion (RACE). The net effect is a progressive loss of lung volume with secondary ventilator-induced lung injury (VILI). Previous concepts of ARDS pathophysiology envisioned a two-compartment system: a small amount of normally aerated lung tissue in the non-dependent regions (termed “baby lung”); and a collapsed and edematous tissue in dependent regions. Based on such compartmentalization, two protective ventilation strategies have been developed: (1) a “protective lung approach” (PLA), designed to reduce overdistension in the remaining aerated compartment using a low tidal volume; and (2) an “open lung approach” (OLA), which first attempts to open the collapsed lung tissue over a short time frame (seconds or minutes) with an initial recruitment maneuver, and then stabilize newly recruited tissue using titrated positive end-expiratory pressure (PEEP). A more recent understanding of ARDS pathophysiology identifies regional alveolar instability and collapse (i.e., hidden micro-atelectasis) in both lung compartments as a primary VILI mechanism. Based on this understanding, we propose an alternative strategy to ventilating the injured lung, which we term a “stabilize lung approach” (SLA). The SLA is designed to immediately stabilize the lung and reduce RACE while gradually reopening collapsed tissue over hours or days. At the core of SLA is time-controlled adaptive ventilation (TCAV), a method to adjust the parameters of the airway pressure release ventilation (APRV) modality. Since the acutely injured lung at any given airway pressure requires more time for alveolar recruitment and less time for alveolar collapse, SLA adjusts inspiratory and expiratory durations and inflation pressure levels. The TCAV method SLA reverses the open first and stabilize second OLA method by: (i) immediately stabilizing lung tissue using a very brief exhalation time (≤0.5 s), so that alveoli simply do not have sufficient time to collapse. The exhalation duration is personalized and adaptive to individual respiratory mechanical properties (i.e., elastic recoil); and (ii) gradually recruiting collapsed lung tissue using an inflate and brake ratchet combined with an extended inspiratory duration (4–6 s) method. Translational animal studies, clinical statistical analysis, and case reports support the use of TCAV as an efficacious lung protective strategy.

A polarization stabilization control system based on digital signal processor (DSP) is proposed in this paper. The system uses low frequency radio frequency (RF) power as control signal for polarization stabilization, and it does not need high-speed circuit to track fast polarization change. Modified particle swarm optimization algorithm is utilized and the effectiveness of polarization stabilization control is experimentally verified.

Estrogen receptor α (ERα) is the most common clinical marker used for breast cancer prognosis and the classification of breast cancer subtypes. Clinically, patients with estrogen receptor-positive breast cancer can receive endocrine therapy. However, resistance to endocrine therapy has become an urgent clinical problem. A large number of previous studies have proven that posttranslational modification of the estrogen receptor is significantly related to endocrine therapy resistance. RNF2 is a member of the RING finger protein family that functions as an E3 ubiquitin ligase. Several studies have clarified that RNF2 is a critical regulator of ERα transcriptional regulation. In our current study, we identified RNF2 as an important posttranslational modification regulator of the estrogen receptor. RNF2 depletion inhibited breast cancer cell progression and ERα signaling activity. TCGA data analysis indicated that RNF2 was elevated in breast malignancies, while RNF2 depletion could drastically inhibit estrogen response gene expression on a whole-genome scale. TCGA data analysis revealed that RNF2 was positively correlated with ERα target gene expression. Further mechanistic studies showed that RNF2 was mainly localized in the nucleus and associated with ERα. The association increased ERα stability by inhibiting ERα K48-linked polyubiquitination. In conclusion, our study implicates nongenomic regulation by RNF2 on ERα protein stability and suggests that targeting RNF2 could be a promising strategy for breast cancer treatments.

The field of coordination chemistry has undergone rapid transformation from preparation of monometallic complexes to multimetallic complexes. So far numerous multimetallic coordination complexes have been synthesized. Multimetallic coordination complexes with well-defined architectures are often called as metal organic polygons and polyhedra (MOPs). In recent past, MOPs have received tremendous attention due to their potential applicability in various emerging fields. However, the field of coordination chemistry of MOPs often suffer set back due to the instability of coordination complexes particularly in aqueous environment-mostly by aqueous solvent and atmospheric moisture. Accordingly, the fate of the field does not rely only on the water solubilities of newly synthesized MOPs but very much dependent on their stabilities both in solution and solid state. The present review discusses several methodologies to prepare MOPs and investigates their stabilities under various circumstances. Considering the potential applicability of MOPs in sustainable way, several methodologies (remedies) to enhance the stabilities of MOPs are discussed here.

Aortic dissection is the most common of the acute aortic syndromes. Acute aortic dissection remains a highly morbid and potentially lethal condition despite contemporary advances in medical and surgical care. Type B aortic dissection (TBAD) is classified as uncomplicated, uncomplicated with high-risk features, and complicated. The role of thoracic endovascular aortic repair (TEVAR) in uncomplicated TBAD remains uncertain and is the topic of ongoing clinical trials. In most complicated cases, TEVAR is effective at restoring visceral and extremity blood flow. TEVAR has also been shown to arrest hemorrhage in the setting of thoracic aortic rupture. TEVAR has been demonstrated to induce satisfactory remodeling in the covered segment of the thoracic aorta, but progressive enlargement of the visceral aorta has led to a variety of techniques designed to promote remodeling in the uncovered aortic segment. There is a need to better define high-risk features so that treatment can be tailored to specific clinical conditions.