Modeling of Concrete Deterioration under External Sulfate Attack and Drying-Wetting Cycles: A Review.

This paper comprehensively summarizes moisture transport, ion transport, and mechanical damage models applied to concrete under sulfate attack and drying-wetting cycles. It highlights the essential aspects and principles of each model, emphasizing their significance in understanding the movement of moisture and ions, as well as the resulting mechanical damage within the concrete during these degradation processes. The paper critically analyzes the assumptions made in each model, shedding light on their limitations and implications for prediction accuracy.

Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2 model of Parkinson's disease.

Several studies have revealed that midbrain dopamine (DA) neurons, even within a single neuroanatomical area, display heterogeneous properties. In parallel, studies using single cell profiling techniques have begun to cluster DA neurons into subtypes based on their molecular signatures. Recent work has shown that molecularly defined DA subtypes within the substantia nigra (SNc) display distinctive anatomic and functional properties, and differential vulnerability in Parkinson's disease (PD).

LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons.

Haloperidol is used to manage psychotic symptoms in several neurological disorders through mechanisms that involve antagonism of dopamine D2 receptors that are highly expressed in the striatum. Significant side effects of haloperidol, known as extrapyramidal symptoms, lead to motor deficits similar to those seen in Parkinson's disease and present a major challenge in clinical settings. The underlying molecular mechanisms responsible for these side effects remain poorly understood.

A novel antagonist of the CCL5/CCR5 axis suppresses the tumor growth and metastasis of triple-negative breast cancer by CCR5-YAP1 regulation.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC) with a high mortality rate, and few effective therapeutic strategies are available. CCL5/CCR5 is an appealing immunotherapeutic target for TNBC. However, its signaling mechanism is poorly understood and its direct antagonists have not been reported.

Risk factors for recurrent pressure ulcers after reconstructive surgery: A retrospective study in a single medical centre.

Recurrence of pressure ulcers following reconstructive surgery occurs frequently, causing a significant burden on the patient and the public health care system. We assessed risk factors for the recurrence of pressure ulcers based on the experience of a single surgeon at our medical centre. We retrospectively analysed patients admitted to our medical centre with stage III and IV pressure ulcers who underwent reconstructive surgery.

R1441C and G2019S LRRK2 knockin mice have distinct striatal molecular, physiological, and behavioral alterations.

LRRK2 mutations are closely associated with Parkinson's disease (PD). Convergent evidence suggests that LRRK2 regulates striatal function. Here, by using knock-in mouse lines expressing the two most common LRRK2 pathogenic mutations-G2019S and R1441C-we investigated how LRRK2 mutations altered striatal physiology.

Closing the structure-to-function gap for LRRK2.

Variations in the LRRK2 gene represent one of the strongest genetic factors for Parkinson's disease (PD). It has become clear that structural knowledge of the encoded large multidomain LRRK2 protein will cast light on its biological function. The new study from Myasnikov, Zhu, et al.

Genetic association of primary nonresponse to anti-TNFα therapy in patients with inflammatory bowel disease.

Objectives: Primary nonresponse (PNR) to antitumor necrosis factor-α (TNFα) biologics is a serious concern in patients with inflammatory bowel disease (IBD). We aimed to identify the genetic variants associated with PNR.

Patients And Methods: Patients were recruited from outpatient GI clinics and PNR was determined using both clinical and endoscopic findings.

A radiomics-based model for predicting local control of resected brain metastases receiving adjuvant SRS.

Purpose: Adjuvant radiosurgery to the cavities of surgically resected brain metastases provides excellent local tumor control while reducing the risk of deleterious cognitive decline associated with whole brain radiotherapy. A subset of these patients, however, will develop disease recurrence following radiosurgery. In this study, we sought to assess the predictive capability of radiomic-based models, as compared with standard clinical features, in predicting local tumor control.

Pathway-specific dysregulation of striatal excitatory synapses by LRRK2 mutations.

LRRK2 is a kinase expressed in striatal spiny projection neurons (SPNs), cells which lose dopaminergic input in Parkinson's disease (PD). R1441C and G2019S are the most common pathogenic mutations of LRRK2. How these mutations alter the structure and function of individual synapses on direct and indirect pathway SPNs is unknown and may reveal pre-clinical changes in dopamine-recipient neurons that predispose toward disease.

NQO1 regulates mitotic progression and response to mitotic stress through modulating SIRT2 activity.

Previous studies have shown that SIRT2 plays a role in mitosis through deacetylating specific downstream targets. However, the upstream regulation of SIRT2 activity has been relatively unexplored. In this study, we provide evidence that NAD(P)H:quinone oxidoreductase 1 (NQO1) interacts with and activates SIRT2 in an NAD-dependent manner.

Glucocerebrosidase haploinsufficiency in A53T α-synuclein mice impacts disease onset and course.

Mutations in GBA1 encountered in Gaucher disease are a leading risk factor for Parkinson disease and associated Lewy body disorders. Many GBA1 mutation carriers, especially those with severe or null GBA1 alleles, have earlier and more progressive parkinsonism. To model the effect of partial glucocerebrosidase deficiency on neurological progression in vivo, mice with a human A53T α-synuclein (SNCA) transgene were crossed with heterozygous null gba mice (gba).

(R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model.

Mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation.

(G2019S) LRRK2 causes early-phase dysfunction of SNpc dopaminergic neurons and impairment of corticostriatal long-term depression in the PD transgenic mouse.

Twelve- to sixteen-month-old (G2019S) LRRK2 transgenic mice prepared by us displayed progressive neuronal death of substantia nigra pars compacta (SNpc) dopaminergic cells. In the present study, we hypothesized that prior to a late-phase death of SNpc dopaminergic neurons, (G2019S) LRRK2 also causes an early-phase neuronal dysfunction of SNpc dopaminergic cells in the (G2019S) LRRK2 mouse. Eight to nine-month-old (G2019S) LRRK2 transgenic mice exhibited the symptom of hypoactivity in the absence of the degeneration of SNpc dopaminergic neurons or nigrostriatal dopaminergic terminals.