The Egf-Ras-Erk Pathway and the Nkx-5/hmx Homeodomain Protein Mls-2 Promote Tube Development in the C.elegans Excretory System

Tubular epithelial cells are one of the most abundant cell types in multicellular organisms. Tubular cells transport gases and liquids, and funnel harmful excretory waste from our bodies. It is clear that Receptor Tyrosine Kinase (RTK) signaling is essential for the formation of many tubular organs such as our kidneys and blood vessels. However, which steps in tube development require RTK signaling is less well understood. The C.elegans excretory system is a primitive renal system with just three essential cells (duct, pore, and canal cells), providing a simple yet dynamic system to study tube specification and morphogenesis. In the C.elegans excretory system, we demonstrated that the EGF-Ras-Erk signaling pathway specified the excretory duct tube versus the pore tube fate. In addition, EGF-Ras-Erk signaling influenced the positions that the duct and pore cells adopted within the tubular network. And finally, after position and fate determination, EGF-Ras-Erk signaling had a continued role in maintaining organ architecture of the duct tube. Goals for future research will be to determine how EGF-Ras-ERK signaling controls these genetically distinct steps during tube development. In a separate project, I studied the Nkx5 homeodomain transcription factor, MLS-2, which was identified in a mutagenesis screen by a former graduate student in the lab. I discovered a role for MLS-2 in promoting proper cell shape of the duct and pore. mls-2 cooperated with the EGF-Ras-Erk pathway to turn on lin-48/Ovo during duct morphogenesis. I speculate that MLS-2 and other Nkx5 family members have conserved functions in promoting shape acquisition in cells that adopt complex morphologies similar to the duct and pore

Teaching the Tough Stuff: The Opportunities and Challenges in Teaching Implicit Bias, Diversity and Inclusion to Supervising Attorneys

We entrust supervising attorneys with the critical responsibility of providing law students with a meaningful experiential learning experience. Supervising attorneys ultimately control the nature of work students receive, the delivery of feedback, and the work environment that the student inhabits. Thus, it is vital that we equip our supervising attorneys with the basic skills necessary to navigate student supervision effectively. Among those basic skills is the ability to traverse the cross-cultural complexities inherent in working with students whose cultural identities may differ from the supervising attorney. Equally important are the cross-cultural issues that may arise among students and the clients and other persons with whom they interact during their externship. This session will discuss the significance in providing supervising training that focuses on diversity and implicit bias as it relates to students, supervision and the externship context. As externship faculty and staff, we have an integral role in ensuring that our supervising attorneys create a working environment for our students that is devoid of discrimination and bias. The standard “supervising attorney training” provides the ideal forum to introduce cultural diversity and implicit bias concepts to supervising attorneys. In such a setting, externship faculty and staff can train supervising attorneys in cross-cultural pedagogy, and expose practitioners to best practices regarding cultural complexities that may arise in student supervision. However, the forum is not without its challenges. Supervising attorney training sessions only allow a limited time to present such an essential, multifaceted issue. Additionally, supervisor training typically consists of a diverse group of attendees, with varying degrees of understanding of diversity and inclusion issues, and who may be uncomfortable delving into seemingly controversial cultural conversations with strangers. The co-presenters will share their experiences in planning and delivering such training, exploring the effectiveness of various methodologies

Beyond somatosensation: Mrgprs in mucosal tissues

Mas-related G coupled receptors (Mrgprs) are a superfamily of receptors expressed in sensory neurons that are known to transmit somatic sensations from the skin to the central nervous system. Interestingly, Mrgprs have recently been implicated in sensory and motor functions of mucosal-associated neuronal circuits. The gastrointestinal and pulmonary tracts are constantly exposed to noxious stimuli. Therefore, it is likely that neuronal Mrgpr signaling pathways in mucosal tissues, akin to their family members expressed in the skin, might relay messages that alert the host when mucosal tissues are affected by damaging signals. Further, Mrgprs have been proposed to mediate the cross-talk between sensory neurons and immune cells that promotes host-protective functions at barrier sites. Although the mechanisms by which Mrgprs are activated in mucosal tissues are not completely understood, these exciting studies implicate Mrgprs as potential therapeutic targets for conditions affecting the intestinal and airway mucosa. This review will highlight the central role of Mrgpr signaling pathways in the regulation of homeostasis at mucosal tissues

Improving pain assessment in mice and rats with advanced videography and computational approaches

Accurately measuring pain in humans and rodents is essential to unravel the neurobiology of pain and discover effective pain therapeutics. However, given its inherently subjective nature, pain is nearly impossible to objectively assess. In the clinic, patients can articulate their pain experience using questionnaires and pain scales but self-reporting can be unreliable due to various psychological and social influences or difficulties for some patients to verbalize their experience (eg, infants, toddlers, and those with neurodevelopmental disorders). At the bench, these challenges are even more daunting as researchers rely on the behaviors of rodents to measure pain or pain relief. Given this, there is a growing realization among pain researchers, clinicians, and funding entities that these traditional approaches of assessing pain in rodents may be flawed. Importantly, these flaws may have contributed to several failed drugs that initially showed promise as analgesics and point toward inconsistencies in our understanding of basic pain neurobiology

Intrashelf basin record of redox and productivity changes along the Arabian margin of Neo-Tethys during Oceanic Anoxic Event 1a

The biotic, environmental, climatic, oceanic, and sea-level perturbations during the Early Aptian Oceanic Anoxic Event (OAE) 1a have been extensively documented from both deep- and shallow-marine deposits worldwide. However, there has been relatively little comparative assessment of the simultaneous interplay among organic carbon burial, redox conditions, terrigenous output, and productivity, leading to a lack of precise constraints on these relationships. Here, we use analyses of stable carbon isotopes (δ13Corg, δ13Ccarb, and Δ13C), total organic carbon (TOC), detrital proxies (Al, Si, Ti, K), redox-sensitive (RSTE: U, V, Mo) and productive-sensitive (PSTE: P, Cu, Ni) trace elements from a continuous, predominantly carbonate succession of the Kazhdumi Intrashelf Basin to evaluate the culprits for the OAE1a-associated changes in bottom-water oxygenation, organic-rich layer formation, and biotic shifts along the Arabian margin of the Neo-Tethys. Concentrations of Al-normalized RSTE and TOC values indicate that the bottom water conditions ranged from oxic prior to and at the onset of the OAE 1a (carbon-isotope segments C2 to basalmost C4 sensu Menegatti et al., 1998), to anoxic-suboxic but not euxinic (Mo 100 m), continental-margin basins during major oceanic perturbations

Phytotoxic characterization of crude methanolic extract of Periploca aphylla

Periploca aphylla is traditionally used in the treatment of various ailments. Phytotoxic activity of crude methanolic extract of P. aphylla was tested on the germination of wheat seeds and on the growth of the germinated seedlings. In both the field and plate studies, the extract showed inhibitory effect on the germination of the growth of root and shoot of the seedlings. The inhibition was found to be dose dependent. The higher concentration of 1000 μg/ml showed maximum inhibitory effect on the growth of root and shoots in the studies of plate as well as on fresh and dry weight of wheat plant. Similarly, the herbicidal activity is also dependent on the concentration of extract. In this study, it was found that inhibitory potential of methanolic extract of P. aphylla increased as 1000 >100 >10 μg/ml.Keywords: Phytotoxic activity, herbicidal activity, germination, plates and field studies, Perifloca aphyll

Evoked and Spontaneous Pain Assessment During Tooth Pulp Injury

Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain. © 2020, The Author(s)

Bacteriological investigation of ground water sources in selected urban areas of district Mardan, Khyber Pakhtunkhwa, Pakistan

Microbial contamination of ground water sources is a common problem in all the big cities, which endangers health and impairs quality of living . To assess this, 39 water samples were collected from highly populated 13 union councils from the urban area of district Mardan. Faecal coliform and Escherichia coli were investigated both qualitatively and quantitatively. Qualitative study showed that faecal coliform was found in 90% samples and E. coli in 56% samples. Quantitatively, faecal coliform most probable number (MPN) was ranging from 1601 to 2400 for about 28% samples, followed by 551 to 1600 and 201 to 550 for 20% samples each, 40 to 200 for 18% samples and less than 40 for about 13% samples. The major cause of the bacteriological contamination was found to be the extent of susceptibility of the water sources to intrusions from the nearest contamination source.Keywords: Mardan, urban area, microbial contamination, faecal coliform, ground water, Escherichia col

The NM23-H1/H2 homolog NDK-1 is required for full activation of Ras signaling in C. elegans

The group I members of the Nm23 (non-metastatic) gene family encode nucleoside diphosphate kinases (NDPKs) that have been implicated in the regulation of cell migration, proliferation and differentiation. Despite their developmental and medical significance, the molecular functions of these NDPKs remain ill defined. To minimize confounding effects of functional compensation between closely related Nm23 family members, we studied ndk-1, the sole Caenorhabditis elegans ortholog of group I NDPKs, and focused on its role in Ras/mitogen-activated protein kinase (MAPK)-mediated signaling events during development. ndk-1 inactivation leads to a protruding vulva phenotype and affects vulval cell fate specification through the Ras/MAPK cascade. ndk-1 mutant worms show severe reduction of activated, diphosphorylated MAPK in somatic tissues, indicative of compromised Ras/MAPK signaling. A genetic epistasis analysis using the vulval induction system revealed that NDK-1 acts downstream of LIN-45/Raf, but upstream of MPK-1/MAPK, at the level of the kinase suppressors of ras (KSR-1/2). KSR proteins act as scaffolds facilitating Ras signaling events by tethering signaling components, and we suggest that NDK-1 modulates KSR activity through direct physical interaction. Our study reveals that C. elegans NDK-1/Nm23 influences differentiation by enhancing the level of Ras/MAPK signaling. These results might help to better understand how dysregulated Nm23 in humans contributes to tumorigenesis. © 2013. Published by The Company of Biologists Ltd

Role of deep brain stimulation (DBS) in addiction disorders

Background: Addiction disorders pose significant challenges to public health, necessitating innovative treatments. This assesses deep brain stimulation (DBS) as a potential intervention for addiction disorders. Methods: A literature review was carried out with a focus on the role of DBS in addiction disorders and its future implications in neurosurgical research. Results: The online literature shows that DBS precisely modulates certain brain regions to restore addiction-related neural circuits and promote behavioral control. Conclusion: Preclinical evidence demonstrates DBS’s potential to rebalance neural circuits associated with addiction, and early clinical trials provide encouraging outcomes in enhancing addiction-related outcomes. Ethical considerations, long-term safety, and personalized patient selection require further investigation