An updated survey of freshwater fishes within Letchworth State Park and surrounding area's of the Genesee River.

The goal of this study was to gather information about freshwater fishes in Letchworth State Park (42.615275° N, -77.992825° W), a portion of New York State-owned land located in the Genesee River Watershed that lacks known data about its fish diversity. Fish collection took place between 2017 and 2019 in the Genesse River upstream and downstream of the falls using electrofishing, gill, hoop, and seine netting. This was the first attempt at a comprehensive survey of this portion of the river, which allowed for a baseline to be established regarding fish biodiversity in the region. The updated total number of species found in this portion of the Genesee River was 25, 22 of which were newly identified downstream of the falls in Letchworth State Park. We encourage further collection and continuation of this survey with consistent sampling techniques to raise awareness about the importance of freshwater fish diversity in stream ecosystems across the globe.

Contaminated sediment in the Detroit River provokes acclimated responses in wild brown bullhead (Ameiurus nebulosus) populations.

In a previous study, adaptive responses to a single polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), were identified in brown bullhead (Ameiurus nebulosus) captured from contaminated sites across the Great Lakes. The tumor suppressor p53 and phase I toxin metabolizing CYP1A genes showed a elevated and refractory response, respectively, up to the F1 generation (Williams and Hubberstey, 2014). As an extension to the first study, bullhead were exposed to sediment collected from sites along the Detroit River to see if these adaptive responses are attainable when fish from a contaminated site are exposed to a mixture of contaminants, instead of a single compound. p53 and CYP1A proteins were measured again with the addition of phase II glutathione-s-transferase (GST) activity in the present study. Three treatment groups were measured: acute (treated immediately), cleared (depurated for three months and subsequent treatment), and farm raised F1 offspring. All three treatment groups were exposed to clean and contaminated sediment for 24 and 96 h. Acute fish from contaminated sites exposed to contaminated sediment revealed an initial elevated p53 response that did not persist in fish after long-term contaminated sediment exposure. Acute fish from contaminated sites exposed to contaminated sediment revealed refractory CYP1A expression, which disappeared in cleared fish and whose F1 response overlapped with clean site F1 offspring. Decreasing GST activity was evident in both clean and contaminated fish over time, and only clean site fish responded to long-term contaminated sediment deliberately with increasing GST activity. Because p53 and CYP1A gene expression and GST activity responses did not overlap between contaminated fish treatment groups, our study suggests that contaminated fish have acclimated to the contaminants present in their environments and no evidence of adaptation could be detected within these biomarkers.

"Infiltrative" Versus "Mass-Forming" Pancreatic Cancer: A New Radiological Classification System for Pancreatic Head Ductal Carcinoma and Its Pathological Correlation.

Purpose: Resectability in localized pancreatic ductal adenocarcinoma (PDAC) is deemed through radiological criteria. Despite initial evaluation classifying tumors as "resectable," they often have ill-defined borders that can result in more extensive cancer than predicted on final pathology analysis. We attempt to categorize these tumors radiologically and define them as "infiltrative" and contrast them to more well-defined or "mass-forming" tumors and assess their correlation with surgical oncological outcomes. We hypothesize that mass-forming lesions will result in fewer positive resection margins. Methods: Patients diagnosed with PDAC of the head of the pancreas and who underwent subsequent curative intent resection between 2016 and 2018 were included. A retrospective chart review of patients was conducted and computed tomography images at the time of diagnosis were reviewed by two radiologists and scored as "mass forming" or "infiltrative" using a newly developed classification system. These classifications were then correlated with margin status. Results: Sixty-eight consecutive pancreatoduodenectomies performed for PDAC from 2016 to 2018 were identified. After screening, 54 patients were eligible for inclusion. Radiologically defined mass-forming lesions had a trend toward a lower rate of positive resection margins (35.7% vs. 50.0%; p = 0.18), specifically the bile duct margin and pancreas margin as well as an overall larger size (4.03 cm vs. 3.25 cm, p = 0.02) compared with infiltrative lesions. Conclusion: We propose a new radiological definition of PDAC into "mass forming" and "infiltrative," a nomenclature that resonates with other tumor sites. Infiltrative lesions trended toward a higher rate of positive resection margins. This classification may help tailor therapy for infiltrative tumors toward a neoadjuvant approach even if they appear resectable.

Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs Against Human Coronavirus 229E (HCoV-229E).

Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5'-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC50 value of 0.07 µM against HCoV-229E with TC50 of > 2.00 µM against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5'-O-fatty acyl conjugates of NRTIs, 5'-O-tetradecanoyl ester conjugate of FTC showed modest activity with EC50 and TC50 values of 72.8 µM and 87.5 µM, respectively. These data can be used for the design of potential compounds against other coronaviruses.

An unusual case of a coexistent serous cystadenoma and intraductal papillary mucinous neoplasm of pancreas. EUS to the rescue!

CONTEXT: Synchronous cystic neoplasms of pancreas are a highly rare occurrence. CASE REPORT: We report a very rare case of coexistent serous cystadenoma and multi-side branch intraductal papillary mucinous neoplasm (IPMN). CONCLUSION: To our knowledge, there has been only one previous case report in the literature of a synchronous serous cystadenoma and a solitary IPMN lesion. This case report is intended to increase the awareness of this condition while alluding to the need for diligent examination by endosonographers. It also highlights the clinical impact of endosonography on the diagnosis and management of cystic legions in the pancreas.

Ocular pathology in acquired immunodeficiency syndrome.

Gross and microscopic ocular findings were prospectively studied in 38 human immunodeficiency virus (HIV)-seropositive subjects undergoing postmortem examination. Pathologic lesions were detected in 27 patients (71%), with 67% of the abnormal findings detected only microscopically.

Dissociation of visual, motor and predictive signals in parietal cortex during visual guidance.

The role of the posterior parietal cortex (PPC) in the visual guidance of movements was studied in monkeys trained to use a joystick to guide a spot to a target. Visual and motor influences were dissociated by transiently occluding the spot and by varying the relationship between the direction of joystick and spot movements. We found a strong segregation of function in PPC during visual guidance. Neurons in area MST were selectively modulated by the direction of visible moving stimuli, whereas neurons in area MIP were selectively modulated by the direction of hand movement. In contrast, the selectivity of cells in the lateral intraparietal area (LIP) did not directly depend on either visual input or motor output, but rather seemed to encode a predictive representation of stimulus movement. These predictive signals may be an important link in visuomotor transformations.

Visual response latencies of magnocellular and parvocellular LGN neurons in macaque monkeys.

Signals relayed through the magnocellular layers of the LGN travel on axons with faster conduction speeds than those relayed through the parvocellular layers. As a result, magnocellular signals might reach cerebral cortex appreciably before parvocellular signals. The relative speed of these two channels cannot be accurately predicted based solely on axon conduction speeds, however. Other factors, such as different degrees of convergence in the magnocellular and parvocellular channels and the retinal circuits that feed them, can affect the time it takes for magnocellular and parvocellular signals to activate cortical neurons. We have investigated the relative timing of visual responses mediated by the magnocellular and parvocellular channels. We recorded individually from 78 magnocellular and 80 parvocellular neurons in the LGN of two anesthetized monkeys. Visual response latencies were measured for small spots of light of various intensities. Over a wide range of stimulus intensities the fastest magnocellular response latencies preceded the fastest parvocellular response latencies by about 10 ms. Because parvocellular neurons are far more numerous than magnocellular neurons, convergence in cortex could reduce the magnocellular advantage by allowing parvocellular signals to generate detectable responses sooner than expected based on the responses of individual parvocellular neurons. An analysis based on a simple model using neurophysiological data collected from the LGN shows that convergence in cortex could eliminate or reverse the magnocellular advantage. This observation calls into question inferences that have been made about ordinal relationships of neurons based on timing of responses.

Neuronal correlates of inferred motion in primate posterior parietal cortex.

For many types of behaviours, it is necessary to monitor the position or movement of objects that are temporarily occluded. The primate posterior parietal cortex contains neurons that are active during visual guidance tasks: in some cases, even if the visual target disappears transiently. It has been proposed that activity of this sort could be related to current or planned eye movements, but it might also provide a more generalized abstract representation of the spatial disposition of targets, even when they are not visible. We have recorded from monkey posterior parietal cortex while the animal viewed a visual stimulus that disappeared, and then, depending on experimental context, could be inferred to be either moving or stationary. During this temporary absence of the stimulus, about half of the neurons were found to be significantly more active on those trials in which the stimulus could be presumed to be moving rather than stationary. The activity was thus present in the absence of either sensory input or motor output, suggesting that it may indeed constitute a generalized representation of target motion.

An active motor model for adaptation by vertebrate hair cells.

Bullfrog saccular hair cells adapt to maintained displacements of their stereociliary bundles by shifting their sensitive range, suggesting an adjustment in the tension felt by the transduction channels. It has been suggested that steady-state tension is regulated by the balance of two calcium-sensitive processes: passive "slipping" and active "tensioning." Here we propose a mathematical model for an adaptation motor that regulates tension, and describe some quantitative tests of the model. Slipping and tensioning rates were determined at membrane potentials of -80 and +80 mV. With these, the model predicts that the I(X) curve (relating bundle displacement and channel open probability) should shift negatively by 124 nm when the cell is depolarized, with an exponential time course that is slower on depolarization from -80 to +80 mV than on repolarization. This was observed: on depolarization, the I(X) curve shifted by an average of 139 nm, and displayed the expected difference in rates at the two potentials. Because the negative shift of the I(X) curve on depolarization represents an increase in the tension on transduction channels, the model also predicts this tension should cause an unrestrained bundle to pivot negatively by 99 nm on depolarization. Such movement was observed using high-resolution video microscopy; its amplitude was variable but ranged up to about 100 nm, and its time course was asymmetric in the same way as that of the I(X) curve shift. In additional comparisons, the active bundle movements and I(X) curve shift exhibited a similar steady-state voltage dependence, and were both reversibly abolished by reduced bath Ca2+ or by the transduction channel blocker streptomycin. Lastly, among different cells, the amplitude of the movement increased with the size of the transduction current. Thus, a quantitative mechanical model for adaptation also accounts for the observed mechanical behavior of the bundle, suggesting that the same mechanism is responsible for both, and that adaptation is mediated by an active, force-producing mechanism.

Tip-link integrity and mechanical transduction in vertebrate hair cells.

An attractive hypothesis for hair-cell transduction is that fine, filamentous "tip links" pull directly on mechanically sensitive ion channels located at the tips of the stereocilia. We tested the involvement of tip links in the transduction process by treating bundles with a BAPTA-buffered, low-Ca2+ saline (10(-9) M). BAPTA abolished the transduction current in a few hundred milliseconds. BAPTA treatment for a few seconds eliminated the tip links observed by either scanning or transmission electron microscopy. BAPTA also eliminated the voltage-dependent movement and caused a positive bundle displacement of 133 nm, in quantitative agreement with a model for regulation of tension. We conclude that tip links convey tension to the transduction channels of hair cells.

Regulation of tension on hair-cell transduction channels: displacement and calcium dependence.

An epithelial preparation of the bullfrog sacculus was used to characterize the initial rate of the adaptation mechanism in hair cells and its dependence on displacement and calcium. The I(X) curve relating transduction current and bundle displacement shifted along the X-axis without substantial change in slope, as previously observed, suggesting that adaptation involves a change in the attachment point of the elastic element connected to ion channels. If the "tip links" model of transduction is correct, this implies that one end of the link moves along the side of the stereocilium. The rates were highly asymmetric: in the tensioning direction the rate was roughly constant at 1-2 microns/sec (calculated as motion along a stereocilium); this is similar to that of myosin on actin. In the relaxing direction it appeared linearly dependent on tension. Calcium preferentially potentiated the relaxation, and apparently reduced the resting tension in the elastic element. The calcium site appears specific for calcium, as other divalent cations inhibited its action. Dihydrostreptomycin inhibited the positive rate, but its effect could not be explained by a simple channel block, and it seems inconsistent with screening of negative charge in the mouth of the transduction channel.

Voltage dependence of adaptation and active bundle movement in bullfrog saccular hair cells.

Hair cells of the bullfrog sacculus adapt to maintained displacement stimuli in a manner that suggests an active regulation of the tension stimulus reaching transduction channels. We have examined adaptation in dissociated hair cells by whole-cell patch-clamp recording and video microscopy. Adaptation was present in these cells, and it depended on extracellular calcium. The adaptation rate--as well as the position of the resting current-displacement curve--also depended on membrane potential, suggesting that calcium passes into the cytoplasm to reach its site of action. After abrupt hyperpolarization, the adaptation rate increased within milliseconds, suggesting that the calcium site is within a few micrometers of the ion channels through which calcium enters. The voltage dependence of the resting current-displacement curve, together with the "gating springs" hypothesis for transduction, predicts movement of the bundle away from the kinocilium when the cell is depolarized. This was observed.

Urotensin II lowers cytoplasmic free calcium concentration in goby enterocytes: measurements using quin2.

A technique is described for the measurement of cytoplasmic free calcium concentration ([Ca2+]c) in a suspension of goby intestinal epithelial cells using the fluorescent probe quin2. For 18 cell suspensions, [Ca2+]c was determined to be 142 +/- 14 nM. The caudal neurosecretory peptide urotensin II at 10(-7) to 10(-6) M concentration reduced [Ca2+]c by 20-50%. Together with previous findings linking the calcium-calmodulin system with the stimulation of Na+ and Cl- absorption in this tissue, it appears that alterations in cytoplasmic Ca2+ may mediate urotensin II-induced stimulation of ion transport.