Progranulin and TDP-43: Mechanistic Links and Future Directions

Loss-of-function mutations in the multifunctional growth factor progranulin (GRN) cause frontotemporal lobar degeneration (FTLD) with TDP-43 protein accumulation. Nuclear TDP-43 protein with key roles in RNA metabolism is also aggregated in amyotrophic lateral sclerosis (ALS), suggesting that ALS and FTLD constitute a broad disease continuum. However, the fact that mutations in GRN are associated with FTLD, while mutations in TDP-43 cause a preferential loss of motor neurons resulting in ALS-end of the disease spectrum, suggests involvement of both cell-autonomous and non-autonomous mechanisms. Studies on animal models and in vitro studies have been instrumental in understanding the link between GRN and TDP-43 and also their role in neurodegeneration. For instance, in mouse models, allelic deficiencies of Grn do not recapitulate human pathology of TDP-43 brain accumulations, but embryonic neurons derived from these mice do show abnormal TDP-43 accumulation after additional cellular challenges, suggesting that TDP-43 changes observed in GRN mutation carriers might also relate to stress. Recent results have shown that the dual action of GRN in growth modulation and inflammation could be due to its negative regulation of TNF-α signaling. In addition, GRN also interacts with sortilin and is endocytosed, thereby regulating its own levels and possibly also modulating the turnover of other proteins including that of TDP-43. Accumulating evidence suggests that TDP-43 abnormal cellular aggregation causes a possible gain of function, also suggested by recently constructed mouse models of TDP-43 proteinopathy; however, it would be inconvincible that sequestration of physiological TDP-43 within cellular aggregates observed in patients would be innocuous for disease pathogenesis. This review discusses some of these data on the possible link between GRN and TDP-43 as well as mechanisms involved in TDP-43-led neurodegeneration. Continued multitiered efforts on genetic, cell biological, and animal modeling approaches would prove crucial in finding a cure for GRN-related diseases

Assessment of various cognitive domains in patient with obsessive-compulsive disorder

Background: OCD is often chronic disorder and causes impairment of functional efficiency. Various researchers have found that cognitive dysfunction frequently present even when mild symptoms are present. This study aimed to investigate various domains of cognitive function in patients with OCD using cross sectional design. In this study we have tried to find out the various domains of cognitive function in OCD and their relation with clinical severities. We also compared the cognitive function of patients with OCD and their control. Methods: Total 60 subjects (30 in case group and 30 in control group) were taken for study. The study subjects (OCD group) were taken from psychiatric OPD and control group from general populations. The subjects of both the groups were screened as per inclusion and exclusion criteria and the Y-BOCS, ACE –III scales were applied. Results: In the case group, 96.70% had a normal ACE-III score and 3.30% had an inconclusive score, while in the control group 100% had a normal score at ACE-III scale, on further scoring. 60% patients have moderate and 33.3% have severe score in the YBOCS scale. We have found the significant decline in total mean ACE-III scores between case and control group (p value 0.000) and decline in memory domain with severity of illness was also significant (p value 0.037). Conclusions: Decline in cognition domain of memory in patient with OCD, was significant in comparison to control group

In vivo and In vitro Interactions between Pseudomonas aeruginosa and Staphylococcus spp.

The significance of polymicrobial infections is increasingly being recognized especially in a biofilm context wherein multiple bacterial species—including both potential pathogens and members of the commensal flora—communicate, cooperate, and compete with each other. Two important bacterial pathogens that have developed a complex network of evasion, counter-inhibition, and subjugation in their battle for space and nutrients are Pseudomonas aeruginosa and Staphylococcus aureus. Their strain- and environment-specific interactions, for instance in the cystic fibrosis lung or in wound infections, show severe competition that is generally linked to worse patient outcomes. For instance, the extracellular factors secreted by P. aeruginosa have been shown to subjugate S. aureus to persist as small colony variants (SCVs). On the other hand, data also exist where S. aureus inhibits biofilm formation by P. aeruginosa but also protects the pathogen by inhibiting its phagocytosis. Interestingly, such interspecies interactions differ between the planktonic and biofilm phenotype, with the extracellular matrix components of the latter likely being a key, and largely underexplored, influence. This review attempts to understand the complex relationship between P. aeruginosa and Staphylococcus spp., focusing on S. aureus, that not only is interesting from the bacterial evolution point of view, but also has important consequences for our understanding of the disease pathogenesis for better patient management

Tau is central in the genetic Alzheimer-frontotemporal dementia spectrum

In contrast to the common and genetically complex senile form of Alzheimer's disease (AD), the molecular genetic dissection of inherited presenile dementias has given important mechanistic insights into the pathogenesis of degenerative brain disease. Here, we focus on recent genotype-phenotype correlative studies in presenile AD and the frontotemporal dementia (FTD) complex of disorders. Together, these studies suggest that AD and FTD are linked in a genetic spectrum of presenile degenerative brain disorders in which tau appears to be the central player

A study on evaluation of ASHAs for their knowledge, attitude and practice towards newborn care in Howrah district of West Bengal

Background: : Accredited Social Health Activist (ASHA) is a trained female community health activist. ASHAs are local women trained to act as facilitator and promoters of health care in their communities. ASHA is trained to work as an interface between the community and the public health system. ASHA play an important role in newborn care to reduce their morbidity and mortality.Methods: Data were collected from ASHAs working in Shibbur area of Howrah District, west Bengal. The study sample consisted of 70 ASHAs working in the Shibpur area that fulfilled the inclusion criteria. A predesigned pretested questionnaire of ASHA was used to collect data in the study.Results: The mean age of ASHAs was 35.74 years. Only 32 (45.71%) had received middle level (class VIII) education. Only 45.71 % of ASHAs had good knowledge and practice regarding hypothermia and its complication and the procedure of providing warmth the baby after delivery. Only 57.1% of ASHA had good knowledge regarding counseling and problem solving on breast feeding. Only 38.57% had good knowledge and practices on identification and basic skill on management of Low Birth Weight (LBW) having birth weight of <2.5kg and pre-term baby (<37 weeks of gestation).Conclusions: In the present study, we found that Knowledge, Attitude and Practice of ASHAs were inadequate in some aspects of newborn care. This gap of knowledge should be taken seriously during training procedures so that effective knowledge and essential skill for newborn care can be imparted. During recruitment of ASHAs higher literally status should be given preferences

Water Droplet Bouncing on a non-Superhydrophobic Si Nanosprings

Self-cleaning surfaces often make use of superhydrophobic coatings that repel water. Here, we report a hydrophobic Si nanospring surface, that effectively suppresses wetting by repelling water droplets. We investigated the dynamic response of Si nanospring arrays fabricated by glancing angle deposition. The vertical standing nanospring arrays were approximately 250 nm tall and 60 nm apart, which allowed the droplets to rebound within a few milliseconds after contact. Amazingly, the morphology of the nanostructures influences the impact dynamics. The rebound time and coefficient of restitution were also found to be higher for Si nanosprings than vertical SI columns. It has been proposed that the restoring force of the Si nanosprings may be responsible for the water droplet rebound and can be explained by considering the droplet/nanospring surface as a coupled spring system. These nanospring surfaces may find applications in self-cleaning windows, liquid-repellent exteriors, glass panels of solar cells, and antifouling agents for roof tiling.Comment: 19 pages, 5 figures, 2 table

Consolidating and Exploring Antibiotic Resistance Gene Data Resources

The unrestricted use of antibiotics has resulted in rapid acquisition of antibiotic resistance (AR) and spread of multidrug-resistant (MDR) bacterial pathogens. With the advent of next-generation sequencing technologies and their application in understanding MDR pathogen dynamics, it has become imperative to unify AR gene data resources for easy accessibility for researchers. However, due to the absence of a centralized platform for AR gene resources, availability, consistency, and accuracy of information vary considerably across different databases. In this article, we explore existing AR gene data resources in order to make them more visible to the clinical microbiology community, to identify their limitations, and to propose potential solutions